Malignant melanoma—The cradle of anti-neoplastic immunotherapy

Critical Reviews in Oncology/Hematology

Volumn 106, Issue , 2016, Pages 25-54

  Koller, Kristian M ^a   Wang, Wenge ^a   Schell, Todd D ^a   Cozza, Eugene M ^a   Kokolus, Kathleen M ^a   Neves, Rogerio I ^a   Mackley, Heath B ^a   Pameijer, Colette ^a   Leung, Anna ^a   Anderson, Bryan ^a   Mallon, Carol A ^a   Robertson, Gavin ^a   Drabick, Joseph J ^a  

^a PENN STATE MILTON S HERSHEY MEDICAL CENTER   (United States)

Author keywords

CTLA 4; History; Immunotherapy; Interferon; Interleukin 2; Melanoma; PD 1; Vaccine

Indexed keywords

ALPHA INTERFERON; ANTINEOPLASTIC AGENT; BCG VACCINE; CYTOKINE; CYTOTOXIC AGENT; CYTOTOXIC T LYMPHOCYTE ANTIGEN 4 INHIBITOR; IMMUNOMODULATING AGENT; IMMUNOSTIMULATING AGENT; INDOLEAMINE 2,3 DIOXYGENASE INHIBITOR; INTERLEUKIN 2; IPILIMUMAB; LYMPHOCYTE ACTIVATION GENE 3 INHIBITOR; MELANOMA VACCINE; PROGRAMMED DEATH PATHWAY ANTAGONIST; ROSE BENGAL; TALIMOGENE LAHERPAREPVEC; TUMOR ANTIGEN; UNCLASSIFIED DRUG; VEMURAFENIB;

ADJUVANT THERAPY; ADOPTIVE TRANSFER; CANCER ADJUVANT THERAPY; CANCER COMBINATION CHEMOTHERAPY; CANCER IMMUNIZATION; CANCER IMMUNOTHERAPY; CANCER RADIOTHERAPY; CANCER RESISTANCE; CANCER SURGERY; HUMAN; IMMUNE DEFICIENCY; IMMUNE RESPONSE; IMMUNOCOMPETENT CELL; IMMUNOREGULATION; IMMUNOSURVEILLANCE; LYMPHOCYTE FUNCTION; MELANOMA; METASTASIS; MICROMETASTASIS; MONOTHERAPY; NONHUMAN; PHENOTYPE; RADIATION RESPONSE; RADIOIMMUNOTHERAPY; REVIEW; SYSTEMIC THERAPY; T LYMPHOCYTE; TUMOR ESCAPE; ANIMAL; IMMUNOLOGY; IMMUNOTHERAPY; PROCEDURES; SKIN NEOPLASMS;

ANIMALS; HUMANS; IMMUNOTHERAPY; MELANOMA; SKIN NEOPLASMS;

EID: 84994834554     PISSN: 10408428     EISSN: 18790461     Source Type: Journal    
DOI: 10.1016/j.critrevonc.2016.04.010     Document Type: Review

References (361)

1. Abbas, A., Lichtman, A.H., Pillai, S., Cellular and molecular immunology. Prop. Overv. Immune Responses, 2014, 1–12.
2. Aebersold, P., et al. Lysis of autologous melanoma cells by tumor-infiltrating lymphocytes: association with clinical response. J. Natl. Cancer Inst. 83:13 (1991), 932–937.
3. Agarwala, S.S., et al. Mature results of a phase III randomized trial of bacillus Calmette-Guerin (BCG) versus observation and BCG plus dacarbazine versus BCG in the adjuvant therapy of American Joint Committee on Cancer Stage I-III melanoma (E1673): a trial of the Eastern Oncology Group. Cancer 100:8 (2004), 1692–1698.
4. Agata, Y., et al. Expression of the PD-1 antigen on the surface of stimulated mouse T and B lymphocytes. Int. Immunol. 8:5 (1996), 765–772.
5. Ahmadzadeh, M., et al. FOXP3 expression accurately defines the population of intratumoral regulatory T cells that selectively accumulate in metastatic melanoma lesions. Blood 112:13 (2008), 4953–4960.
6. Ahmadzadeh, M., et al. Tumor antigen-specific CD8 T cells infiltrating the tumor express high levels of PD-1 and are functionally impaired. Blood 114:8 (2009), 1537–1544.
7. Almand, B., et al. Increased production of immature myeloid cells in cancer patients: a mechanism of immunosuppression in cancer. J. Immunol. 166:1 (2001), 678–689.
8. Anon, A Phase I. Trial of a Vaccine Combining Multiple Class I Peptides and Montanide ISA 51VG With Escalating Doses of Anti-PD-1 Antibody Nivolumab or Ipilimumab With Nivolumab For Patients With Resected Stages IIIC/IV Melanoma − Full Text View − ClinicalTrials.gov. 2014 (Available from: https://clinicaltrials.gov/ct2/show/NCT01176474?term=nivolumab+adjuvant&rank=1).
9. Anon, Safety study of anti-LAG-3 with and without anti-PD-1. The Treatment of Solid Tumors − Full Text View − ClinicalTrials.gov, 2014 (Available from: https://clinicaltrials.gov/ct2/show/NCT01968109?term=LAG-3&rank=3).
10. Anon, Multiple Class I Peptides & Montanide ISA. 51 VG W Escalating Doses of Anti-PD-1 Ab BMS936558 − Full Text View − ClinicalTrials.gov. 2014 (Available from: https://clinicaltrials.gov/ct2/show/NCT01176461?term=nivolumab +adjuvant&rank=2).
11. Anon, Neoadjuvant Combination Therapy With Ipilimumab and HighDose IFN-α2b for Melanoma − Full Text View − ClinicalTrials.gov. (2014; Available from:) http://clinicaltrials.gov/ct2/show/NCT01608594?term=ipilimumab+neoadjuvant&rank=6.
12. Apetoh, L., et al. Toll-like receptor 4-dependent contribution of the immune system to anticancer chemotherapy and radiotherapy. Nat. Med. 13:9 (2007), 1050–1059.
13. Appay, V., The physiological role of cytotoxic CD4(+) T-cells: the holy grail?. Clin. Exp. Immunol., 2004, 10–13 (England).
14. Ascierto, P.A., Marincola, F.M., Ribas, A., Anti-CTLA4 monoclonal antibodies: the past and the future in clinical application. J. Trans. Med. Engl., 2011, 196.
15. Attia, P., et al. Inability of a fusion protein of IL-2 and diphtheria toxin (Denileukin Diftitox: DAB389IL-2, ONTAK) to eliminate regulatory T lymphocytes in patients with melanoma. J. Immunother. 28:6 (2005), 582–592.
16. Baars, J.W., et al. Treatment with tumour infiltrating lymphocytes and interleukin-2 in patients with metastatic melanoma: a pilot study. Biotherapy 4:4 (1992), 289–297.
17. Baitsch, L., et al. Exhaustion of tumor-specific CD8(+) T cells in metastases from melanoma patients. J. Clin. Invest. 121:6 (2011), 2350–2360.
18. Bajetta, E., et al. Multicenter randomized trial of dacarbazine alone or in combination with two different doses and schedules of interferon alfa-2a in the treatment of advanced melanoma. J. Clin. Oncol. 12:4 (1994), 806–811.
19. Baker, J.J., et al. Systematic review: surgery for patients with metastatic melanoma during active treatment with ipilimumab. Am. Surg. 80:8 (2014), 805–810.
20. Barker, C.A., Postow, M.A., Combinations of radiation therapy and immunotherapy for melanoma: a review of clinical outcomes. Int. J. Radiat. Oncol. Biol. Phys. 88:5 (2014), 986–997.
21. Barker, C.A., et al. Concurrent radiotherapy and ipilimumab immunotherapy for patients with melanoma. Cancer Immunol. Res. 1:2 (2013), 92–98.
22. Barnett, B., et al. Regulatory T cells in ovarian cancer: biology and therapeutic potential. Am. J. Reprod. Immunol. 54:6 (2005), 369–377.
23. Baurain, J.F., et al. High frequency of autologous anti-melanoma CTL directed against an antigen generated by a point mutation in a new helicase gene. J. Immunol. 164:11 (2000), 6057–6066.
24. Becker, M.R., et al. COX-2 expression in malignant melanoma: a novel prognostic marker?. Melanoma Res. 19:1 (2009), 8–16.
25. Bennett, W., Some peculiarities in the behavior of certain malignant and innocent growths. Lancet 1 (1899), 227–241.
26. Berd, D., et al. Activation markers on T cells infiltrating melanoma metastases after therapy with dinitrophenyl-conjugated vaccine. Cancer Immunol. Immunother. 39:3 (1994), 141–147.
27. Besser, M.J., et al. Adoptive transfer of tumor-infiltrating lymphocytes in patients with metastatic melanoma: intent-to-treat analysis and efficacy after failure to prior immunotherapies. Clin. Cancer Res. 19:17 (2013), 4792–4800.
28. Bjorkman, P.J., et al. Structure of the human class I histocompatibility antigen: HLA-A2. Nature 329:6139 (1987), 506–512.
29. Bjorkman, P.J., et al. The foreign antigen binding site and T cell recognition regions of class I histocompatibility antigens. Nature 329:6139 (1987), 512–518.
30. Blackburn, S.D., et al. Coregulation of CD8+ T cell exhaustion by multiple inhibitory receptors during chronic viral infection. Nat. Immunol. 10:1 (2009), 29–37.
31. Bodurtha, A.J., et al. A clinical histologic: and immunologic study of a case of metastatic malignant melanoma undergoing spontaneous remission. Cancer 37:2 (1976), 735–742.
32. Boni, A., et al. Selective BRAFV600E inhibition enhances T-cell recognition of melanoma without affecting lymphocyte function. Cancer Res. 70:13 (2010), 5213–5219.
33. Bronte, V., Zanovello, P., Regulation of immune responses by L-arginine metabolism. Nat. Rev. Immunol. 5:8 (2005), 641–654.
34. Bronte, V., et al. Identification of a CD11b(+)/Gr-1(+)/CD31(+) myeloid progenitor capable of activating or suppressing CD8(+) T cells. Blood 96:12 (2000), 3838–3846.
35. Bruns, P., Die heilwirkung des erysipels auf gescwulste. Beitr. Klin. Chir. 3 (1888), 443–466.
36. Bullani, R.R., et al. Frequent downregulation of Fas (CD95) expression and function in melanoma. Melanoma Res. 12:3 (2002), 263–270.
37. Burmeister, B.H., et al. Adjuvant radiotherapy versus observation alone for patients at risk of lymph-node field relapse after therapeutic lymphadenectomy for melanoma: a randomised trial. Lancet Oncol. 13:6 (2012), 589–597.
38. Burnet, M., Cancer: a biological approach. III. Viruses associated with neoplastic conditions. IV. Practical applications. Br. Med. J. 1:5023 (1957), 841–847.
39. Burnet, F.M., The concept of immunological surveillance. Prog. Exp. Tumor Res. 13 (1970), 1–27.
40. Buzaid, A.C., et al. Phase II study of neoadjuvant concurrent biochemotherapy in melanoma patients with local-regional metastases. Melanoma Res. 8:6 (1998), 549–556.
41. Bystryn, J.C., et al. Relationship between immune response to melanoma vaccine immunization and clinical outcome in stage II malignant melanoma. Cancer 69:5 (1992), 1157–1164.
42. Camisaschi, C., et al. LAG-3 expression defines a subset of CD4(+)CD25(high)Foxp3(+) regulatory T cells that are expanded at tumor sites. J. Immunol. 184:11 (2010), 6545–6551.
43. Camisaschi, C., et al. Alternative activation of human plasmacytoid DCs in vitro and in melanoma lesions: involvement of LAG-3. J. Invest. Dermatol. 134:7 (2014), 1893–1902.
44. Casares, N., et al. Caspase-dependent immunogenicity of doxorubicin-induced tumor cell death. J. Exp. Med. 202:12 (2005), 1691–1701.
45. Chang, C.C., et al. Immune selection of hot-spot beta 2-microglobulin gene mutations: HLA-A2 allospecificity loss, and antigen-processing machinery component down-regulation in melanoma cells derived from recurrent metastases following immunotherapy. J. Immunol. 174:3 (2005), 1462–1471.
46. Chapon, M., et al. Progressive upregulation of PD-1 in primary and metastatic melanomas associated with blunted TCR signaling in infiltrating T lymphocytes. J. Invest. Dermatol. 131:6 (2011), 1300–1307.
47. Chavan, R., et al. Untreated stage IV melanoma patients exhibit abnormal monocyte phenotypes and decreased functional capacity. Cancer Immunol. Res. 2:3 (2014), 241–248.
48. Chiba, S., et al. Tumor-infiltrating DCs suppress nucleic acid-mediated innate immune responses through interactions between the receptor TIM-3 and the alarmin HMGB1. Nat. Immunol. 13:9 (2012), 832–842.
49. Cipponi, A., et al. Tumor-infiltrating lymphocytes: apparently good for melanoma patients. But why?. Cancer Immunol. Immunother. 60:8 (2011), 1153–1160.
50. Clemente, C.G., et al. Prognostic value of tumor infiltrating lymphocytes in the vertical growth phase of primary cutaneous melanoma. Cancer 77:7 (1996), 1303–1310.
51. Cole, D.J., et al. Histopathological analysis of metastatic melanoma deposits in patients receiving adoptive immunotherapy with tumor-infiltrating lymphocytes. Cancer Immunol. Immunother. 38:5 (1994), 299–303.
52. Cole, W.H., Efforts to explain spontaneous regression of cancer. J. Surg. Oncol. 17:3 (1981), 201–209.
53. Coley, W.B., Hoguet, J.P., Melanotic cancer: with a report of 91cases. Ann. Surg. 64:2 (1916), 206–241.
54. Coley, W.B., II: contribution to the knowledge of sarcoma. Ann. Surg. 14:3 (1891), 199–220.
55. Coley, W., The treatment of malignant tumors by repeated inoculations of erysipelas with a report of ten original cases. Am. J. Med. Sci. 105 (1893), 487–511.
56. Coley, W., Treatment of inoperable malignant tumors with the toxins of erysipelas and the Bacillus prodigiosus. Trans. Am. Surg. Assoc. 12 (1894), 183–212.
57. Coley, W., Late results of the treatment of inoperable sarcoma by the mixed toxins of erysipelas and Bacillus prodigiosus. Am. J. Med. Sci. 131 (1906), 375–430.
58. Comin-Anduix, B., et al. The oncogenic BRAF kinase inhibitor PLX4032/RG7204 does not affect the viability or function of human lymphocytes across a wide range of concentrations. Clin. Cancer Res. 16:24 (2010), 6040–6048.
59. Coulie, P.G., et al. A mutated intron sequence codes for an antigenic peptide recognized by cytolytic T lymphocytes on a human melanoma. Proc. Natl. Acad. Sci. U. S. A. 92:17 (1995), 7976–7980.
60. Coulie, P.G., et al. Tumour antigens recognized by T lymphocytes: at the core of cancer immunotherapy. Nat. Rev. Cancer 14:2 (2014), 135–146.
61. Coventry, B.J., et al. CRP identifies homeostatic immune oscillations in cancer patients: a potential treatment targeting tool?. J. Transl. Med., 7, 2009, p102.
62. Creagan, E.T., et al. Adjuvant radiation therapy for regional nodal metastases from malignant melanoma: a randomized, prospective study. Cancer 42:5 (1978), 2206–2210.
63. Curiel, T.J., Regulatory T cells and treatment of cancer. Curr. Opin. Immunol. 20:2 (2008), 241–246.
64. Damian, D.L., Saw, R.P., Thompson, J.F., Topical immunotherapy with diphencyprone for in transit and cutaneously metastatic melanoma. J. Surg. Oncol. 109:4 (2014), 308–313.
65. Daponte, A., et al. Phase III randomized study of fotemustine and dacarbazine versus dacarbazine with or without interferon-alpha in advanced malignant melanoma. J. Transl. Med., 11, 2013, 38.
66. Deng, L., et al. STING-dependent cytosolic DNA sensing promotes radiation-induced type I interferon-dependent antitumor immunity in immunogenic tumors. Immunity 41:5 (2014), 843–852.
67. Devos, R., et al. Molecular cloning of human interleukin 2 cDNA and its expression in E. coli. Nucleic Acids Res. 11:13 (1983), 4307–4323.
68. Dewey, D.L., The radiosensitivity of melanoma cells in culture. Br. J. Radiol. 44:526 (1971), 816–817.
69. Diamond, M.S., et al. Type I interferon is selectively required by dendritic cells for immune rejection of tumors. J. Exp. Med. 208:10 (2011), 1989–2003.
70. Diener-West, M., et al. The COMS randomized trial of iodine 125 brachytherapy for choroidal melanoma, III: initial mortality findings. COMS Report No. 18. Arch. Ophthalmol. 119:7 (2001), 969–982.
71. Dikov, M.M., et al. Vascular endothelial growth factor effects on nuclear factor-kappaB activation in hematopoietic progenitor cells. Cancer Res. 61:5 (2001), 2015–2021.
72. Disis, M.L., Bernhard, H., Jaffee, E.M., Use of tumour-responsive T cells as cancer treatment. Lancet 373:9664 (2009), 673–683.
73. Dong, H., et al. Tumor-associated B7-H1 promotes T-cell apoptosis: a potential mechanism of immune evasion. Nat. Med. 8:8 (2002), 793–800.
74. Dudley, M.E., et al. Adoptive transfer of cloned melanoma-reactive T lymphocytes for the treatment of patients with metastatic melanoma. J. Immunother. 24:4 (2001), 363–373.
75. Dudley, M.E., et al. Cancer regression and autoimmunity in patients after clonal repopulation with antitumor lymphocytes. Science 298:5594 (2002), 850–854.
76. Dudley, M.E., et al. Adoptive cell therapy for patients with metastatic melanoma: evaluation of intensive myeloablative chemoradiation preparative regimens. J. Clin. Oncol. 26:32 (2008), 5233–5239.
77. Dunn, G.P., Old, L.J., Schreiber, R.D., The immunobiology of cancer immunosurveillance and immunoediting. Immunity 21:2 (2004), 137–148.
78. Durham, N.M., et al. Lymphocyte activation gene 3 (LAG-3) modulates the ability of CD4 T-cells to Be suppressed In vivo. PLoS One, 9(11), 2014, e109080.
79. Eberle, J., Hossini, A.M., Expression and function of bcl-2 proteins in melanoma. Curr. Genom. 9:6 (2008), 409–419.
80. Eggermont, A.M., et al. Adjuvant therapy with pegylated interferon alfa-2b versus observation alone in resected stage III melanoma: final results of EORTC 18991, a randomised phase III trial. Lancet 372:9633 (2008), 117–126.
81. Eggermont, A.M., et al. Long-term results of the randomized phase III trial EORTC 18991 of adjuvant therapy with pegylated interferon alfa-2b versus observation in resected stage III melanoma. J. Clin. Oncol. 30:31 (2012), 3810–3818.
82. Eggermont, A.M., et al. Adjuvant ganglioside GM2-KLH/QS-21 vaccination versus observation after resection of primary tumor >1.5 mm in patients with stage II melanoma: results of the EORTC 18961 randomized phase III trial. J. Clin. Oncol. 31:30 (2013), 3831–3837.
83. Eggermont, A., Ipilimumab versus placebo after complete resection of stage III melanoma: initial efficacy and safety results from the EORTC 18071 phase III trial. J. Clin. Oncol., 2014 (ABSTRACT).
84. Ehrlich, P., Uber den jetzigen stand der karzinomforschung. Ne. Tijdschr Geneeskd 5 (1909), 273–290.
85. Engels, B., Rowley, D.A., Schreiber, H., Targeting stroma to treat cancers. Semin. Cancer Biol. 22:1 (2012), 41–49.
86. Erdag, G., et al. Immunotype and immunohistologic characteristics of tumor-infiltrating immune cells are associated with clinical outcome in metastatic melanoma. Cancer Res. 72:5 (2012), 1070–1080.
87. Everson, T., Cole, W., Anonymous Spontaneous Regression of Cancer. 1966, WB Saunders Co., Philadelphia.
88. Everson, T.C., Spontaneous regression of cancer. Ann N. Y. Acad. Sci. U. S. A. 114 (1964), 721–735.
89. Falkson, C.I., Falkson, G., Falkson, H.C., Improved results with the addition of interferon alfa-2b to dacarbazine in the treatment of patients with metastatic malignant melanoma. J. Clin. Oncol. 9:8 (1991), 1403–1408.
90. Falkson, C.I., et al. Phase III trial of dacarbazine versus dacarbazine with interferon alpha-2b versus dacarbazine with tamoxifen versus dacarbazine with interferon alpha-2b and tamoxifen in patients with metastatic malignant melanoma: an Eastern Cooperative Oncology Group study. J. Clin. Oncol. 16:5 (1998), 1743–1751.
91. Fateh, S., et al. Unsuccessful high dose IL-2 therapy followed immediately by near continuous low dose temozolomide can result in rapid durable complete and near-complete remissions in metastatic melanoma. Cancer Biol. Ther. 10:11 (2010), 1091–1097.
92. Fife, B.T., et al. Interactions between PD-1 and PD-L1 promote tolerance by blocking the TCR-induced stop signal. Nat. Immunol. 10:11 (2009), 1185–1192.
93. Filipazzi, P., et al. Identification of a new subset of myeloid suppressor cells in peripheral blood of melanoma patients with modulation by a granulocyte-macrophage colony-stimulation factor-based antitumor vaccine. J. Clin. Oncol. 25:18 (2007), 2546–2553.
94. Finkelstein, S.E., et al. The florida melanoma trial I: a prospective multicenter phase I/II trial of postoperative hypofractionated adjuvant radiotherapy with concurrent interferon-Alfa-2b in the treatment of advanced stage III melanoma with long-Term toxicity follow-Up. ISRN Immunol., 2012, 10.
95. Flaherty, K.T., et al. Improved survival with MEK inhibition in BRAF-mutated melanoma. N. Engl. J. Med. 367:2 (2012), 107–114.
96. Flaherty, L.E., et al. Southwest oncology group S0008: a phase III trial of high-Dose interferon alfa-2b versus cisplatin, vinblastine, and dacarbazine DTIC, plus interleukin-2 and interferon in patients with high-Risk melanoma-An intergroup study of cancer and leukemia group B, children's oncology group, eastern cooperative oncology group, and southwest oncology group. J. Clin. Oncol., 2014.
97. Foss, F.M., DAB(389)IL-2 (denileukin diftitox, ONTAK): a new fusion protein technology. Clin. Lymphoma 1:Suppl. 1 (2000), S27–S31.
98. Fourcade, J., et al. Upregulation of Tim-3 and PD-1 expression is associated with tumor antigen-specific CD8+ T cell dysfunction in melanoma patients. J. Exp. Med. 207:10 (2010), 2175–2186.
99. Francisco, L.M., Sage, P.T., Sharpe, A.H., The PD-1 pathway in tolerance and autoimmunity. Immunol. Rev. 236 (2010), 219–242.
100. Freeman, G.J., et al. Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation. J. Exp. Med. 192:7 (2000), 1027–1034.
101. Fregni, G., et al. Phenotypic and functional characteristics of blood natural killer cells from melanoma patients at different clinical stages. PLoS One, 8(10), 2013, e76928.
102. Fritsch, E.F., et al. HLA-Binding properties of tumor neoepitopes in humans. Cancer Immunol. Res. 2:6 (2014), 522–529.
103. Fuertes, M.B., et al. Host type I IFN signals are required for antitumor CD8+ T cell responses through CD8{alpha}+ dendritic cells. J. Exp. Med. 208:10 (2011), 2005–2016.
104. Fyfe, G.A., et al. Long-term response data for 255 patients with metastatic renal cell carcinoma treated with high-dose recombinant interleukin-2 therapy. J. Clin. Oncol. 14:8 (1996), 2410–2411.
105. Gabrilovich, D.I., Nagaraj, S., Myeloid-derived suppressor cells as regulators of the immune system. Nat Rev Immunol 9:3 (2009), 162–174.
106. Gabrilovich, D., et al. Vascular endothelial growth factor inhibits the development of dendritic cells and dramatically affects the differentiation of multiple hematopoietic lineages in vivo. Blood 92:11 (1998), 4150–4166.
107. Gabrilovich, D.I., Ostrand-Rosenberg, S., Bronte, V., Coordinated regulation of myeloid cells by tumours. Nat. Rev. Immunol. 12:4 (2012), 253–268.
108. Gajewski, T.F., et al. Cancer immunotherapy strategies based on overcoming barriers within the tumor microenvironment. Curr. Opin. Immunol. 25:2 (2013), 268–276.
109. Gajewski, T.F., Schreiber, H., Fu, Y.X., Innate and adaptive immune cells in the tumor microenvironment. Nat. Immunol. 14:10 (2013), 1014–1022.
110. Galluzzi, L., et al. Cell death modalities: classification and pathophysiological implications. Cell Death Differ. 14:7 (2007), 1237–1243.
111. Gao, Q., et al. Intratumoral balance of regulatory and cytotoxic T cells is associated with prognosis of hepatocellular carcinoma after resection. J. Clin. Oncol. 25:18 (2007), 2586–2593.
112. Garrido, C., et al. MHC class I molecules act as tumor suppressor genes regulating the cell cycle gene expression: invasion and intrinsic tumorigenicity of melanoma cells. Carcinogenesis 33:3 (2012), 687–693.
113. Gartner, J.J., et al. Comparative exome sequencing of metastatic lesions provides insights into the mutational progression of melanoma. BMC Genom., 13, 2012, 505.
114. Gattinoni, L., et al. Removal of homeostatic cytokine sinks by lymphodepletion enhances the efficacy of adoptively transferred tumor-specific CD8+ T cells. J. Exp. Med. 202:7 (2005), 907–912.
115. Gibbs, P., et al. A phase II study of neoadjuvant biochemotherapy for stage III melanoma. Cancer 94:2 (2002), 470–476.
116. Goedegebuure, P.S., et al. Adoptive immunotherapy with tumor-infiltrating lymphocytes and interleukin-2 in patients with metastatic malignant melanoma and renal cell carcinoma: a pilot study. J. Clin. Oncol. 13:8 (1995), 1939–1949.
117. Gooden, M.J., et al. The prognostic influence of tumour-infiltrating lymphocytes in cancer: a systematic review with meta-analysis. Br. J. Cancer 105:1 (2011), 93–103.
118. Gresser, I.A., Chekhov, M.D., Coley's toxins. N. Engl. J. Med., 317(7), 1987, p457.
119. Grimaldi, A.M., et al. Abscopal effects of radiotherapy on advanced melanoma patients who progressed after ipilimumab immunotherapy. Oncoimmunology, 3, 2014, pe28780.
120. Grimm, E.A., et al. Lymphokine-activated killer cell phenomenon: lysis of natural killer-resistant fresh solid tumor cells by interleukin 2-activated autologous human peripheral blood lymphocytes. J. Exp. Med. 155:6 (1982), 1823–1841.
121. Grimm, E.A., et al. Lymphokine-activated killer cell phenomenon: III Evidence that IL-2 is sufficient for direct activation of peripheral blood lymphocytes into lymphokine-activated killer cells. J. Exp. Med. 158:4 (1983), 1356–1361.
122. Groom, J.R., Luster, A.D., CXCR3 ligands: redundant, collaborative and antagonistic functions. Immunol. Cell Biol. 89:2 (2011), 207–215.
123. Gros, A., et al. Myeloid cells obtained from the blood but not from the tumor can suppress T-cell proliferation in patients with melanoma. Clin. Cancer Res. 18:19 (2012), 5212–5223.
124. Gros, A., et al. PD-1 identifies the patient-specific CD8(+) tumor-reactive repertoire infiltrating human tumors. J. Clin. Invest. 124:5 (2014), 2246–2259.
125. Gross, L., Intradermal immunization of C3H mice against sarcoma that originated in an animal of the same line. Cancer Res. 3 (1943), 326–333.
126. Hamblin, T.J., Interleukin 2. BMJ 300:6720 (1990), 275–276.
127. Hamid, O., et al. Safety and tumor responses with lambrolizumab (anti-PD-1) in melanoma. N. Engl. J. Med. 369:2 (2013), 134–144.
128. Hannier, S., et al. CD3/TCR complex-associated lymphocyte activation gene-3 molecules inhibit CD3/TCR signaling. J. Immunol. 161:8 (1998), 4058–4065.
129. Harlin, H., et al. Chemokine expression in melanoma metastases associated with CD8+ T-cell recruitment. Cancer Res. 69:7 (2009), 3077–3085.
130. Harwood, A.R., Conventional fractionated radiotherapy for 51 patients with lentigo maligna and lentigo maligna melanoma. Int. J. Radiat. Oncol. Biol. Phys. 9:7 (1983), 1019–1021.
131. Hauschild, A., et al. Dabrafenib in BRAF-mutated metastatic melanoma: a multicentre, open-label, phase 3 randomised controlled trial. Lancet 380:9839 (2012), 358–365.
132. Havas, H.F., et al. Clinical results and immunologic effects of a mixed bacterial vaccine in cancer patients. Med. Oncol. Tumor Pharmacother. 10:4 (1993), 145–158.
133. Hedblad, M.A., Mallbris, L., Grenz ray treatment of lentigo maligna and early lentigo maligna melanoma. J. Am. Acad. Dermatol. 67:1 (2012), 60–68.
134. Hemmi, H., et al. A toll-like receptor recognizes bacterial DNA. Nature 408:6813 (2000), 740–745.
135. Hemon, P., et al. MHC class II engagement by its ligand LAG-3 (CD223) contributes to melanoma resistance to apoptosis. J. Immunol. 186:9 (2011), 5173–5183.
136. Herin, M., et al. Production of stable cytolytic T-cell clones directed against autologous human melanoma. Int. J. Cancer 39:3 (1987), 390–396.
137. Hernberg, M., et al. Tumor-infiltrating lymphocytes in patients with metastatic melanoma receiving chemoimmunotherapy. J. Immunother. 20:6 (1997), 488–495.
138. Hinrichs, C.S., Rosenberg, S.A., Exploiting the curative potential of adoptive T-cell therapy for cancer. Immunol. Rev. 257:1 (2014), 56–71.
139. Ho, P.C., et al. Immune-based antitumor effects of BRAF inhibitors rely on signaling by CD40L and IFNgamma. Cancer Res. 74:12 (2014), 3205–3217.
140. Hodi, F.S., et al. Improved survival with ipilimumab in patients with metastatic melanoma. N. Engl. J. Med. 363:8 (2010), 711–723.
141. Hodi, F.S., et al. Ipilimumab plus sargramostim vs ipilimumab alone for treatment of metastatic melanoma: a randomized clinical trial. JAMA 312:17 (2014), 1744–1753.
142. Homet, B., Ribas, A., New drug targets in metastatic melanoma. J. Pathol. 232:2 (2014), 134–141.
143. Hsueh, E.C., et al. Does endogenous immune response determine the outcome of surgical therapy for metastatic melanoma?. Ann. Surg. Oncol. 7:3 (2000), 232–238.
144. Hsueh, E.C., et al. Prolonged survival after complete resection of disseminated melanoma and active immunotherapy with a therapeutic cancer vaccine. J. Clin. Oncol. 20:23 (2002), 4549–4554.
145. Hu-Lieskovan, S., et al. Combining targeted therapy with immunotherapy in BRAF-mutant melanoma: promise and challenges. J. Clin. Oncol. 32:21 (2014), 2248–2254.
146. Inozume, T., et al. Selection of CD8 + PD-1+ lymphocytes in fresh human melanomas enriches for tumor-reactive T cells. J. Immunother. 33:9 (2010), 956–964.
147. Isaacs, A., Lindenmann, J., Virus interference I. the interferon. by A. isaacs and J. lindenmann, 1957. J. Interferon Res. 7:5 (1987), 429–438.
148. Ives, N.J., et al. Chemotherapy compared with biochemotherapy for the treatment of metastatic melanoma: a meta-analysis of 18 trials involving 2,621 patients. J. Clin. Oncol. 25:34 (2007), 5426–5434.
149. Jacobs, J.F., et al. Dendritic cell vaccination in combination with anti-CD25 monoclonal antibody treatment: a phase I/II study in metastatic melanoma patients. Clin. Cancer Res. 16:20 (2010), 5067–5078.
150. Jacobs, J.F., et al. Regulatory T cells in melanoma: the final hurdle towards effective immunotherapy?. Lancet Oncol. 13:1 (2012), pe32–42.
151. Johnson, L.A., et al. Gene therapy with human and mouse T-cell receptors mediates cancer regression and targets normal tissues expressing cognate antigen. Blood 114:3 (2009), 535–546.
152. Johnson, D.B., et al. Combined BRAF (Dabrafenib) and MEK inhibition (Trametinib) in patients with BRAFV600-mutant melanoma experiencing progression with single-agent BRAF inhibitor. J. Clin. Oncol. 32:33 (2014), 3697–3704.
153. Jones, P.C., et al. Prolonged survival for melanoma patients with elevated IgM antibody to oncofetal antigen. J. Natl. Cancer Inst. 66:2 (1981), 249–254.
154. Kalinski, P., Regulation of immune responses by prostaglandin E2. J. Immunol. 188:1 (2012), 21–28.
155. Kantoff, P.W., et al. Sipuleucel-T immunotherapy for castration-resistant prostate cancer. N. Engl. J. Med. 363:5 (2010), 411–422.
156. Karbach, J., et al. Phase I clinical trial of mixed bacterial vaccine (Coley's toxins) in patients with NY-ESO-1 expressing cancers: immunological effects and clinical activity. Clin. Cancer Res. 18:19 (2012), 5449–5459.
157. Kempin, S., Cirrincione, C., Myers, J., Combined modality therapy of advanced nodular lymphomas: the role of non-specific immunotherapy as an important determinant of response and survival [abstract]. Proc. Am. Soc. Clin. Oncol., 24, 1983, 56.
158. Khong, H.T., Wang, Q.J., Rosenberg, S.A., Identification of multiple antigens recognized by tumor-infiltrating lymphocytes from a single patient: tumor escape by antigen loss and loss of MHC expression. J. Immunother. 27:3 (2004), 184–190.
159. Kidner, T.B., et al. Combined intralesional Bacille Calmette-Guerin (BCG) and topical imiquimod for in-transit melanoma. J. Immunother. 35:9 (2012), 716–720.
160. Kim, G., et al. FDA approval summary: vemurafenib for treatment of unresectable or metastatic melanoma with the BRAFV600E mutation. Clin. Cancer Res. 20:19 (2014), 4994–5000.
161. Kirkwood, J.M., Ernstoff, M.S., Interferons in the treatment of human cancer. J. Clin. Oncol. 2:4 (1984), 336–352.
162. Kirkwood, J.M., et al. Interferon alfa-2b adjuvant therapy of high-risk resected cutaneous melanoma: the Eastern Cooperative Oncology Group Trial EST 1684. J. Clin. Oncol. 14:1 (1996), 7–17.
163. Kirkwood, J.M., et al. High- and low-dose interferon alfa-2b in high-risk melanoma: first analysis of intergroup trial E1690/S9111/C9190. J. Clin. Oncol. 18:12 (2000), 2444–2458.
164. Kirkwood, J.M., et al. High-dose interferon alfa-2b significantly prolongs relapse-free and overall survival compared with the GM2-KLH/QS-21 vaccine in patients with resected stage IIB-III melanoma: results of intergroup trial E1694/S9512/C509801. J. Clin. Oncol. 19:9 (2001), 2370–2380.
165. Ko, H.J., et al. A combination of chemoimmunotherapies can efficiently break self-tolerance and induce antitumor immunity in a tolerogenic murine tumor model. Cancer Res. 67:15 (2007), 7477–7486.
166. Kolmel, K., et al. Treatment of advanced malignant melanoma by a pyrogenic bacterail lystate. A pilot study. Oncologie 14 (1991), 411–417.
167. Kradin, R.L., et al. Tumour-infiltrating lymphocytes and interleukin-2 in treatment of advanced cancer. Lancet 1:8638 (1989), 577–580.
168. Krengli, M., et al. Radiotherapy in the treatment of mucosal melanoma of the upper aerodigestive tract: analysis of 74 cases: A Rare Cancer Network study. Int. J. Radiat. Oncol. Biol. Phys. 65:3 (2006), 751–759.
169. Krieg, A., CpG motifs: the active ingredient in bacterial extracts?. Nat. Med. 9:7 (2003), 831–835.
170. Kroemer, G., et al. Classification of cell death: recommendations of the Nomenclature Committee on Cell Death. Cell Death Differ. 12:Suppl. 2 (2005), 1463–1467.
171. Kroemer, G., et al. Immunogenic cell death in cancer therapy. Annu. Rev. Immunol. 31 (2013), 51–72.
172. Krug, A., et al. Toll-like receptor expression reveals CpG DNA as a unique microbial stimulus for plasmacytoid dendritic cells which synergizes with CD40 ligand to induce high amounts of IL-12. Eur. J. Immunol. 31:10 (2001), 3026–3037.
173. Landsberg, J., et al. Melanomas resist T-cell therapy through inflammation-induced reversible dedifferentiation. Nature 490:7420 (2012), 412–416.
174. Lange, J.R., et al. A pilot study of the combination of interleukin-2-based immunotherapy and radiation therapy. J. Immunother. (1991) 12:4 (1992), 265–271.
175. Larkin, J., et al. Combined nivolumab and ipilimumab or monotherapy in untreated melanoma. N. Engl. J. Med. 373:1 (2015), 23–34.
176. Lathers, D.M., et al. Phase 1B study to improve immune responses in head and neck cancer patients using escalating doses of 25-hydroxyvitamin D3. Cancer Immunol. Immunother. 53:5 (2004), 422–430.
177. Lawson, D.H., Tarhini, A.A., Margolin, K.A., Ernstoff, M.S., Kirkwood, J.M., E4697: Phase III cooperative group study of yeast derived granulocyte/macrophage colony-stimulating factor (GM-CSF) versus placebo as adjuvant treatment of patients with completely resected stage III-IV melanoma. J. Clin. Oncol., 28(Suppl. 85028), 2010.
178. Lee, Y., et al. Therapeutic effects of ablative radiation on local tumor require CD8+ T cells: changing strategies for cancer treatment. Blood 114:3 (2009), 589–595.
179. Leiter, U., et al. Antiapoptotic bcl-2 and bcl-xL in advanced malignant melanoma. Arch. Dermatol. Res. 292:5 (2000), 225–232.
180. Leung, A.M., Hari, D.M., Morton, D.L., Surgery for distant melanoma metastasis. Cancer J. 18:2 (2012), 176–184.
181. Linard, B., et al. A ras-mutated peptide targeted by CTL infiltrating a human melanoma lesion. J. Immunol. 168:9 (2002), 4802–4808.
182. Lindenmann, J., From interference to interferon: a brief historical introduction. Philos. Trans. R Soc. Lond. B Biol. Sci. 299:1094 (1982), 3–6.
183. Lipton, A., et al. Corynebacterium parvum versus bacille Calmette-Guerin adjuvant immunotherapy of stage II malignant melanoma. J. Clin. Oncol. 9:7 (1991), 1151–1156.
184. Liu, X., et al. Selective inhibition of IDO1 effectively regulates mediators of antitumor immunity. Blood 115:17 (2010), 3520–3530.
185. Livingston, P.O., et al. Vaccines containing purified GM2 ganglioside elicit GM2 antibodies in melanoma patients. Proc. Natl. Acad. Sci. U. S. A. 84:9 (1987), 2911–2915.
186. Livingston, P.O., et al. Improved survival in stage III melanoma patients with GM2 antibodies: a randomized trial of adjuvant vaccination with GM2 ganglioside. J. Clin. Oncol. 12:5 (1994), 1036–1044.
187. Long, G.V., et al. Combined BRAF and MEK inhibition versus BRAF inhibition alone in melanoma. N. Engl. J. Med. 371:20 (2014), 1877–1888.
188. Lotze, M.T., et al. In vivo administration of purified human interleukin 2. II. Half life: immunologic effects, and expansion of peripheral lymphoid cells in vivo with recombinant IL 2. J. Immunol. 135:4 (1985), 2865–2875.
189. Lotze, M.T., et al. High-dose recombinant interleukin 2 in the treatment of patients with disseminated cancer. Responses: treatment-related morbidity, and histologic findings. JAMA 256:22 (1986), 3117–3124.
190. Lu, T., Gabrilovich, D.I., Molecular pathways: tumor-infiltrating myeloid cells and reactive oxygen species in regulation of tumor microenvironment. Clin. Cancer Res. 18:18 (2012), 4877–4882.
191. Lu, Y.C., et al. Efficient identification of mutated cancer antigens recognized by T cells associated with durable tumor regressions. Clin. Cancer Res. 20:13 (2014), 3401–3410.
192. Macon-Lemaitre, L., Triebel, F., The negative regulatory function of the lymphocyte-activation gene-3 co-receptor (CD223) on human T cells. Immunology 115:2 (2005), 170–178.
193. Manon, R., et al. Phase II trial of radiosurgery for one to three newly diagnosed brain metastases from renal cell carcinoma, melanoma, and sarcoma: an Eastern Cooperative Oncology Group study (E 6397). J. Clin. Oncol. 23:34 (2005), 8870–8876.
194. Mao, Y., et al. Melanoma-educated CD14+ cells acquire a myeloid-derived suppressor cell phenotype through COX-2-dependent mechanisms. Cancer Res. 73:13 (2013), 3877–3887.
195. Mazumder, A., Lymphokine-activated killer cells: in vitro and in vivo studies. Lymphokine Res. 4:3 (1985), 215–220.
196. Mehnert, J.M., Kluger, H.M., Driver mutations in melanoma: lessons learned from bench-to-bedside studies. Curr. Oncol. Rep. 14:5 (2012), 449–457.
197. Mellor, A.L., Munn, D.H., IDO expression by dendritic cells: tolerance and tryptophan catabolism. Nat. Rev. Immunol. 4:10 (2004), 762–774.
198. Merrouche, Y., et al. Clinical application of retroviral gene transfer in oncology: results of a French study with tumor-infiltrating lymphocytes transduced with the gene of resistance to neomycin. J. Clin. Oncol. 13:2 (1995), 410–418.
199. Mikhail, G.R., Gorsulowsky, D.C., Spontaneous regression of metastatic malignant melanoma. J. Dermatol. Surg. Oncol. 12:5 (1986), 497–500.
200. Mildner, A., Jung, S., Development and function of dendritic cell subsets. Immunity 40:5 (2014), 642–656.
201. Millward, M., et al. Phase I study of tremelimumab (CP-675 206) plus PF-3512676 (CPG 7909) in patients with melanoma or advanced solid tumours. Br. J. Cancer 108:10 (2013), 1998–2004.
202. Mirza, N., et al. All-trans-retinoic acid improves differentiation of myeloid cells and immune response in cancer patients. Cancer Res. 66:18 (2006), 9299–9307.
203. Mitchell, M.S., et al. Randomized trial of an allogeneic melanoma lysate vaccine with low-dose interferon Alfa-2b compared with high-dose interferon Alfa-2b for Resected stage III cutaneous melanoma. J. Clin. Oncol. 25:15 (2007), 2078–2085.
204. Mocellin, S., et al. Interferon alpha for the adjuvant treatment of cutaneous melanoma. Cochrane Database Syst. Rev., 6, 2013 (Cd008955).
205. Molenkamp, B.G., et al. Local administration of PF-3512676CpG-B instigates tumor-specific CD8+ T-cell reactivity in melanoma patients. Clin. Cancer Res. 14:14 (2008), 4532–4542.
206. Molife, R., Hancock, B.W., Adjuvant therapy of malignant melanoma. Crit. Rev. Oncol. Hematol. 44:1 (2002), 81–102.
207. Moretta, A., et al. Inhibitory and activatory receptors for HLA class I molecules in human natural killer cells. Chem. Immunol. 64 (1996), 77–87.
208. Morgan, D.A., Ruscetti, F.W., Gallo, R., Selective in vitro growth of T lymphocytes from normal human bone marrows. Science 193:4257 (1976), 1007–1008.
209. Morgan, R.A., et al. Cancer regression in patients after transfer of genetically engineered lymphocytes. Science 314:5796 (2006), 126–129.
210. Morton, D.L., et al. Immunological factors in human sarcomas and melanomas: a rational basis for immunotherapy. Ann. Surg. 172:4 (1970), 740–749.
211. Morton, D., et al. Immunological factors which influence response to immunotherapy in malignant melanoma. Surgery 68:1 (1970), 158–163 discussion 163–164.
212. Morton, D.L., et al. BCG immunotherapy of malignant melanoma: summary of a seven-year experience. Ann. Surg. 180:4 (1974), 635–643.
213. Morton, D.L., et al. Preliminary results of a randomized trial of adjuvant immunotherapy in patients with malignant melanoma who have lymph node metastases. Aust. N. Z. J. Surg. 48:1 (1978), 49–52.
214. Morton, D.L., et al. Prolongation of survival in metastatic melanoma after active specific immunotherapy with a new polyvalent melanoma vaccine. Ann. Surg. 216:4 (1992), 463–482.
215. Moschos, S.J., et al. Neoadjuvant treatment of regional stage IIIB melanoma with high-dose interferon alfa-2b induces objective tumor regression in association with modulation of tumor infiltrating host cellular immune responses. J. Clin. Oncol. 24:19 (2006), 3164–3171.
216. Muller, K., et al. Fractionated stereotactic radiotherapy for uveal melanoma: late clinical results. Radiother. Oncol. 102:2 (2012), 219–224.
217. Munn, D.H., Mellor, A.L., Indoleamine 2,3-dioxygenase and tumor-induced tolerance. J. Clin. Invest. 117:5 (2007), 1147–1154.
218. Muul, L.M., et al. Identification of specific cytolytic immune responses against autologous tumor in humans bearing malignant melanoma. J. Immunol. 138:3 (1987), 989–995.
219. Nathanson, Spontaneous regression of malignant melanoma: a review of the literature on incidence, clinical features, and possible mechanisms. Natl. Cancer Inst. Monogr. 44 (1976), 67–76.
220. Nauts, H.C., Swift, W.E., Coley, B.L., The treatment of malignant tumors by bacterial toxins as developed by the late William B. Coley M.D., reviewed in the light of modern research. Cancer Res. 6 (1946), 205–216.
221. Nauts, H.C., Fowler, G.A., Bogatko, F.H., A review of the influence of bacterial infection and of bacterial products (Coley's toxins) on malignant tumors in man; a critical analysis of 30 inoperable cases treated by Coley's mixed toxins, in which diagnosis was confirmed by microscopic examination selected for special study. Acta Med. Scand. Suppl. 276 (1953), 1–103.
222. Neville, M.E., Robb, R.J., Popescu, M.C., In situ vaccination against a non-immunogenic tumour using intratumoural injections of liposomal interleukin 2. Cytokine 16:6 (2001), 239–250.
223. Nishikawa, H., Sakaguchi, S., Regulatory T cells in tumor immunity. Int. J. Cancer 127:4 (2010), 759–767.
224. Nishimura, H., et al. Development of lupus-like autoimmune diseases by disruption of the PD-1 gene encoding an ITIM motif-carrying immunoreceptor. Immunity 11:2 (1999), 141–151.
225. Nishimura, H., et al. Autoimmune dilated cardiomyopathy in PD-1 receptor-deficient mice. Science 291:5502 (2001), 319–322.
226. Nowak, A.K., Robinson, B.W., Lake, R.A., Synergy between chemotherapy and immunotherapy in the treatment of established murine solid tumors. Cancer Res. 63:15 (2003), 4490–4496.
227. Obermajer, N., et al. Positive feedback between PGE2 and COX2 redirects the differentiation of human dendritic cells toward stable myeloid-derived suppressor cells. Blood 118:20 (2011), 5498–5505.
228. Oble, D.A., et al. Focus on TILs: prognostic significance of tumor infiltrating lymphocytes in human melanoma. Cancer Immun., 9, 2009, p3.
229. Ochsenbein, A.F., et al. Roles of tumour localization: second signals and cross priming in cytotoxic T-cell induction. Nature 411:6841 (2001), 1058–1064.
230. Okwan-Duodu, D., et al. Role of radiation therapy as immune activator in the era of modern immunotherapy for metastatic malignant melanoma. Am. J. Clin. Oncol. 38:1 (2015), 119–125.
231. Ollila, D.W., Stern, S.L., Morton, D.L., Tumor doubling time: a selection factor for pulmonary resection of metastatic melanoma. J. Surg. Oncol. 69:4 (1998), 206–211.
232. Osler, W., The medical aspects of carcinoma of the breast, with a note on the spontaneous disappearance of secondary growth. Am. Med. 13 (1901), 17–63.
233. Overgaard, J., et al. Hyperthermia as an adjuvant to radiation therapy of recurrent or metastatic malignant melanoma: A multicentre randomized trial by the European Society for Hyperthermic Oncology 1996. Int. J. Hyperthermia 25:5 (2009), 323–334.
234. Ozao-Choy, J., Lee, D.J., Faries, M.B., Melanoma vaccines: mixed past, promising future. Surg. Clin. North Am. 94:5 (2014), 1017–1030 viii.
235. Pardoll, D.M., The blockade of immune checkpoints in cancer immunotherapy. Nat. Rev. Cancer 12:4 (2012), 252–264.
236. Pashenkov, M., et al. Phase II trial of a toll-like receptor 9-activating oligonucleotide in patients with metastatic melanoma. J. Clin. Oncol. 24:36 (2006), 5716–5724.
237. Pico de Coana, Y., et al. Ipilimumab treatment results in an early decrease in the frequency of circulating granulocytic myeloid-derived suppressor cells as well as their Arginase1 production. Cancer Immunol. Res. 1:3 (2013), 158–162.
238. Pietra, G., et al. Melanoma cells inhibit natural killer cell function by modulating the expression of activating receptors and cytolytic activity. Cancer Res. 72:6 (2012), 1407–1415.
239. Pilon-Thomas, S., et al. Efficacy of adoptive cell transfer of tumor-infiltrating lymphocytes after lymphopenia induction for metastatic melanoma. J. Immunother. 35:8 (2012), 615–620.
240. Pockaj, B.A., et al. Localization of 111indium-labeled tumor infiltrating lymphocytes to tumor in patients receiving adoptive immunotherapy: Augmentation with cyclophosphamide and correlation with response. Cancer 73:6 (1994), 1731–1737.
241. Poschke, I., et al. Immature immunosuppressive CD14 + HLA-DR-/low cells in melanoma patients are Stat3hi and overexpress CD80: CD83, and DC-sign. Cancer Res. 70:11 (2010), 4335–4345.
242. Postow, M.A., et al. Immunologic correlates of the abscopal effect in a patient with melanoma. N. Engl. J. Med. 366:10 (2012), 925–931.
243. Postow, M.A., et al. Nivolumab and ipilimumab versus ipilimumab in untreated melanoma. N. Engl. J. Med. 372:21 (2015), 2006–2017.
244. Prehn, R.T., Main, J.M., Immunity to methylcholanthrene-induced sarcomas. J. Natl. Cancer Inst. 18:6 (1957), 769–778.
245. Prieto, P.A., et al. CTLA-4 blockade with ipilimumab: long-term follow-up of 177 patients with metastatic melanoma. Clin. Cancer Res. 18:7 (2012), 2039–2047.
246. Quezada, S.A., et al. Tumor-reactive CD4(+) T cells develop cytotoxic activity and eradicate large established melanoma after transfer into lymphopenic hosts. J. Exp. Med. 207:3 (2010), 637–650.
247. Radny, P., et al. Phase II trial of intralesional therapy with interleukin-2 in soft-tissue melanoma metastases. Br. J. Cancer 89:9 (2003), 1620–1626.
248. Radvanyi, L.G., et al. Specific lymphocyte subsets predict response to adoptive cell therapy using expanded autologous tumor-infiltrating lymphocytes in metastatic melanoma patients. Clin. Cancer Res. 18:24 (2012), 6758–6770.
249. Rajabi, P., et al. The role of VEGF in melanoma progression. J. Res. Med. Sci. 17:6 (2012), 534–539.
250. Ramaekers, B.L., et al. Systematic review and meta-analysis of radiotherapy in various head and neck cancers: comparing photons, carbon-ions and protons. Cancer Treat. Rev. 37:3 (2011), 185–201.
251. Ramakrishnan, R., et al. Chemotherapy enhances tumor cell susceptibility to CTL-mediated killing during cancer immunotherapy in mice. J. Clin. Invest. 120:4 (2010), 1111–1124.
252. Rasku, M.A., et al. Transient T cell depletion causes regression of melanoma metastases. J. Transl. Med., 6, 2008, 12.
253. Rech, A.J., et al. CD25 blockade depletes and selectively reprograms regulatory T cells in concert with immunotherapy in cancer patients. Sci. Transl. Med., 4(134), 2012 (134ra62).
254. Redondo, P., et al. Vascular endothelial growth factor (VEGF) and melanoma: N-acetylcysteine downregulates VEGF production in vitro. Cytokine 12:4 (2000), 374–378.
255. Restifo, N.P., et al. Loss of functional beta 2-microglobulin in metastatic melanomas from five patients receiving immunotherapy. J. Natl. Cancer Inst. 88:2 (1996), 100–108.
256. Ribas, A., et al. Hepatotoxicity with combination of vemurafenib and ipilimumab. N. Engl. J. Med. 368:14 (2013), 1365–1366.
257. Ribas, A., et al. Pembrolizumab versus investigator-choice chemotherapy for ipilimumab-refractory melanoma (KEYNOTE-002): a randomised, controlled, phase 2 trial. Lancet Oncol. 16:8 (2015), 908–918.
258. Ridolfi, L., et al. Radiotherapy as an immunological booster in patients with metastatic melanoma or renal cell carcinoma treated with high-dose Interleukin-2: evaluation of biomarkers of immunologic and therapeutic response. J. Transl. Med., 12, 2014, 262.
259. Robbins, P.F., et al. A mutated beta-catenin gene encodes a melanoma-specific antigen recognized by tumor infiltrating lymphocytes. J. Exp. Med. 183:3 (1996), 1185–1192.
260. Robbins, P.F., et al. Tumor regression in patients with metastatic synovial cell sarcoma and melanoma using genetically engineered lymphocytes reactive with NY-ESO-1. J. Clin. Oncol. 29:7 (2011), 917–924.
261. Robbins, P.F., et al. Mining exomic sequencing data to identify mutated antigens recognized by adoptively transferred tumor-reactive T cells. Nat. Med. 19:6 (2013), 747–752.
262. Robert, C., et al. Ipilimumab plus dacarbazine for previously untreated metastatic melanoma. N. Engl. J. Med. 364:26 (2011), 2517–2526.
263. Robert, C., et al. Anti-programmed-death-receptor-1 treatment with pembrolizumab in ipilimumab-refractory advanced melanoma: a randomised dose-comparison cohort of a phase 1 trial. Lancet 384:9948 (2014), 1109–1117.
264. Robert, C., et al. Nivolumab in previously untreated melanoma without BRAF mutation. N. Engl. J. Med. 372:4 (2015), 320–330.
265. Robert, C., et al. Pembrolizumab versus ipilimumab in advanced melanoma. N. Engl. J. Med. 372:26 (2015), 2521–2532.
266. Rosenberg, S.A., et al. Observations on the systemic administration of autologous lymphokine-activated killer cells and recombinant interleukin-2 to patients with metastatic cancer. N. Engl. J. Med. 313:23 (1985), 1485–1492.
267. Rosenberg, S.A., Spiess, P., Lafreniere, R., A new approach to the adoptive immunotherapy of cancer with tumor-infiltrating lymphocytes. Science 233:4770 (1986), 1318–1321.
268. Rosenberg, S.A., et al. Use of tumor-infiltrating lymphocytes and interleukin-2 in the immunotherapy of patients with metastatic melanoma. A preliminary report. N. Engl. J. Med. 319:25 (1988), 1676–1680.
269. Rosenberg, S.A., et al. Use of tumor-infiltrating lymphocytes and interleukin-2 in the immunotherapy of patients with metastatic melanoma. A preliminary report. N. Engl. J. Med. 319:25 (1988), 1676–1680.
270. Rosenberg, S.A., et al. Prospective randomized trial of high-dose interleukin-2 alone or in conjunction with lymphokine-activated killer cells for the treatment of patients with advanced cancer. J. Natl. Cancer Inst. 85:8 (1993), 622–632.
271. Rosenberg, S.A., et al. Treatment of 283 consecutive patients with metastatic melanoma or renal cell cancer using high-dose bolus interleukin 2. JAMA 271:12 (1994), 907–913.
272. Rosenberg, S.A., et al. Treatment of patients with metastatic melanoma with autologous tumor-infiltrating lymphocytes and interleukin 2. J. Natl. Cancer Inst. 86:15 (1994), 1159–1166.
273. Rosenberg, S.A., et al. Immunologic and therapeutic evaluation of a synthetic peptide vaccine for the treatment of patients with metastatic melanoma. Nat. Med. 4:3 (1998), 321–327.
274. Rosenberg, S.A., et al. Durability of complete responses in patients with metastatic cancer treated with high-dose interleukin-2: identification of the antigens mediating response. Ann. Surg. 228:3 (1998), 307–319.
275. Rosenberg, S.A., et al. Durable complete responses in heavily pretreated patients with metastatic melanoma using T-cell transfer immunotherapy. Clin. Cancer Res. 17:13 (2011), 4550–4557.
276. Rosenberg, S.A., IL-2: the first effective immunotherapy for human cancer. J. Immunol. 192:12 (2014), 5451–5458.
277. Rosenthal, R., et al. Active specific immunotherapy phase III trials for malignant melanoma: systematic analysis and critical appraisal. J. Am. Coll. Surg. 207:1 (2008), 95–105.
278. Roth, J.A., Silverstein, M.J., Morton, D.L., Metastatic potential of metastases. Surgery 79:6 (1976), 669–673.
279. Rotzschke, O., et al. Isolation and analysis of naturally processed viral peptides as recognized by cytotoxic T cells. Nature 348:6298 (1990), 252–254.
280. Ruscetti, F.W., Morgan, D.A., Gallo, R.C., Functional and morphologic characterization of human T cells continuously grown in vitro. J. Immunol. 119:1 (1977), 131–138.
281. Safwat, A., et al. A phase II trial of low-dose total body irradiation and subcutaneous interleukin-2 in metastatic melanoma. Radiother. Oncol. 77:2 (2005), 143–147.
282. Sakaguchi, S., et al. FOXP3+ regulatory T cells in the human immune system. Nat. Rev. Immunol. 10:7 (2010), 490–500.
283. Saleh, F.H., et al. Primary melanoma tumour regression associated with an immune response to the tumour-associated antigen melan-A/MART-1. Int. J. Cancer 94:4 (2001), 551–557.
284. Sanchez-Perez, L., et al. Potent selection of antigen loss variants of B16 melanoma following inflammatory killing of melanocytes in vivo. Cancer Res. 65:5 (2005), 2009–2017.
285. Sato, E., et al. Intraepithelial CD8+ tumor-infiltrating lymphocytes and a high CD8+/regulatory T cell ratio are associated with favorable prognosis in ovarian cancer. Proc. Natl. Acad. Sci. U. S. A. 102:51 (2005), 18538–18543.
286. Sause, W.T., et al. Fraction size in external beam radiation therapy in the treatment of melanoma. Int. J. Radiat. Oncol. Biol. Phys. 20:3 (1991), 429–432.
287. Schilling, B., et al. Vemurafenib reverses immunosuppression by myeloid derived suppressor cells. Int. J. Cancer 133:7 (2013), 1653–1663.
288. Schumacher, L.Y., Ribas, A., Overcoming tumor resistance to immunotherapy. Cancer Ther. 4 (2006), 13–26.
289. Schwartzentruber, D.J., et al. In vitro predictors of therapeutic response in melanoma patients receiving tumor-infiltrating lymphocytes and interleukin-2. J. Clin. Oncol. 12:7 (1994), 1475–1483.
290. Schwartzentruber, D.J., et al. gp100 peptide vaccine and interleukin-2 in patients with advanced melanoma. N. Engl. J. Med. 364:22 (2011), 2119–2127.
291. Sensi, M., Anichini, A., Unique tumor antigens: evidence for immune control of genome integrity and immunogenic targets for T cell-mediated patient-specific immunotherapy. Clin. Cancer Res. 12:17 (2006), 5023–5032.
292. Senzer, N.N., et al. Phase II clinical trial of a granulocyte-macrophage colony-stimulating factor-encoding: second-generation oncolytic herpesvirus in patients with unresectable metastatic melanoma. J. Clin. Oncol. 27:34 (2009), 5763–5771.
293. Seung, S.K.et al., Phase 1 study of stereotactic body radiotherapy and interleukin-2–tumor and immunological responses. Sci. Transl. Med., 4(137), 2012, 137ra74.
294. Shankaran, V., et al. IFNgamma and lymphocytes prevent primary tumour development and shape tumour immunogenicity. Nature 410:6832 (2001), 1107–1111.
295. Sharma, S., et al. Tumor cyclooxygenase 2-dependent suppression of dendritic cell function. Clin. Cancer Res. 9:3 (2003), 961–968.
296. Shear, M., Turner, F., Chemical treatment of tumors: isolation of hemorrhage-producing fraction from Serratia marcescans (Bacillus prodigiosus) culture filtrate. J. Natl. Cancer Inst. 4 (1943), 81–97.
297. Shen, R.N., et al. A comparison of lung metastases and natural killer cell activity in daily fractions and weekly fractions of radiation therapy on murine B16a melanoma. Radiat. Res. 114:2 (1988), 354–360.
298. Shin, M.S., et al. Alterations of Fas (Apo-1/CD95) gene in cutaneous malignant melanoma. Am. J. Pathol. 154:6 (1999), 1785–1791.
299. Slingluff, C.L. Jr., et al. Effect of granulocyte/macrophage colony-stimulating factor on circulating CD8+ and CD4+ T-cell responses to a multipeptide melanoma vaccine: outcome of a multicenter randomized trial. Clin. Cancer Res. 15:22 (2009), 7036–7044.
300. Snyder, A., et al. Genetic basis for clinical response to CTLA-4 blockade in melanoma. N. Engl. J. Med. 371:23 (2014), 2189–2199.
301. Somasundaram, R., Villanueva, J., Herlyn, M., Intratumoral heterogeneity as a therapy resistance mechanism: role of melanoma subpopulations. Adv. Pharmacol. 65 (2012), 335–359.
302. Sondak, V.K., et al. Adjuvant immunotherapy of resected, intermediate-thickness, node-negative melanoma with an allogeneic tumor vaccine: overall results of a randomized trial of the Southwest Oncology Group. J. Clin. Oncol. 20:8 (2002), 2058–2066.
303. Soslow, R.A., et al. COX-2 is expressed in human pulmonary: colonic, and mammary tumors. Cancer 89:12 (2000), 2637–2645.
304. Sosman, J.A., et al. A phase 2 trial of complete resection for stage IV melanoma: results of Southwest Oncology Group Clinical Trial S9430. Cancer, 117(20), 2011 4740–06.
305. Sosman, J.A., et al. Survival in BRAF V600-mutant advanced melanoma treated with vemurafenib. N. Engl. J. Med. 366:8 (2012), 707–714.
306. Sparwasser, T., et al. Bacterial CpG-DNA activates dendritic cells in vivo: t helper cell-independent cytotoxic T cell responses to soluble proteins. Eur. J. Immunol. 30:12 (2000), 3591–3597.
307. Spiess, P.J., Yang, J.C., Rosenberg, S.A., In vivo antitumor activity of tumor-infiltrating lymphocytes expanded in recombinant interleukin-2. J. Natl. Cancer Inst. 79:5 (1987), 1067–1075.
308. Spranger, S., Gajewski, T., Rational combinations of immunotherapeutics that target discrete pathways. J. Immunother. Cancer, 1, 2013, 16.
309. Spranger, S., et al. Mechanism of tumor rejection with doublets of CTLA-4 PD-1/PD-L1, or IDO blockade involves restored IL-2 production and proliferation of CD8(+) T cells directly within the tumor microenvironment. J. Immunother. Cancer, 2, 2014, p3.
310. Spranger, S.et al., Up-regulation of PD-L1, IDO, and T(regs) in the melanoma tumor microenvironment is driven by CD8(+) T cells. Sci. Transl. Med., 5(200), 2013, 200ra116.
311. Stamell, E.F., et al. The abscopal effect associated with a systemic anti-melanoma immune response. Int. J. Radiat. Oncol. Biol. Phys. 85:2 (2013), 293–295.
312. Starnes, C.O., Coley's toxins in perspective. Nature 357:6373 (1992), 11–12.
313. Steinberg, S.M., et al. BRAF inhibition alleviates immune suppression in murine autochthonous melanoma. Cancer Immunol. Res. 2:11 (2014), 1044–1050.
314. Suzuki, E., et al. Gemcitabine selectively eliminates splenic Gr-1+/CD11b+ myeloid suppressor cells in tumor-bearing animals and enhances antitumor immune activity. Clin. Cancer Res. 11:18 (2005), 6713–6721.
315. Takeuchi, O., Akira, S., Pattern recognition receptors and inflammation. Cell 140:6 (2010), 805–820.
316. Taramelli, D., et al. Classes I and II HLA and melanoma-associated antigen expression and modulation on melanoma cells isolated from primary and metastatic lesions. Cancer Res. 46:1 (1986), 433–439.
317. Tarhini, A.A., Thalanayar, P.M., Melanoma adjuvant therapy. Hematol. Oncol. Clin. North Am. 28:3 (2014), 471–489.
318. Tarhini, A.A., Pahuja, S., Kirkwood, J.M., Neoadjuvant therapy for high-risk bulky regional melanoma. J. Surg. Oncol. 104:4 (2011), 386–390.
319. Taube, J.M., et al. Colocalization of inflammatory response with B7-h1 expression in human melanocytic lesions supports an adaptive resistance mechanism of immune escape. Sci. Transl. Med., 4(127), 2012, 127ra37.
320. Telang, S., et al. Phase II trial of the regulatory T cell-depleting agent, denileukin diftitox, in patients with unresectable stage IV melanoma. BMC Cancer, 11, 2011, 515.
321. Temple-Oberle, C.F., et al. Intra-lesional interleukin-2 therapy for in transit melanoma. J. Surg. Oncol. 109:4 (2014), 327–331.
322. Tesniere, A., et al. Immunogenic cancer cell death: a key-lock paradigm. Curr. Opin. Immunol. 20:5 (2008), 504–511.
323. Thomas, L., Discussion. Lawrence, H.S., (eds.) Cellular and Humoral Aspects of the Hypersensitive States, 1959, Hoeber-Harper, New York, 529–532.
324. Thompson, J.F.et al., Phase 2 study of intralesional PV-10 in refractory metastatic melanoma. Ann. Surg. Oncol., 2014.
325. Thomson, D.B., et al. Interferon-alpha 2a does not improve response or survival when combined with dacarbazine in metastatic malignant melanoma: results of a multi-institutional Australian randomized trial. Melanoma Res. 3:2 (1993), 133–138.
326. Toomey, P.et al., Intralesional injection of rose bengal induces a systemic tumor-specific immune response in murine models of melanoma and breast cancer. PLoS One, 8(7), 2013, e68561.
327. Topalian, S.L., et al. Expansion of human tumor infiltrating lymphocytes for use in immunotherapy trials. J. Immunol. Methods 102:1 (1987), 127–141.
328. Topalian, S.L., et al. Safety: activity, and immune correlates of anti-PD-1 antibody in cancer. N. Engl. J. Med. 366:26 (2012), 2443–2454.
329. Tran, K.Q., et al. Minimally cultured tumor-infiltrating lymphocytes display optimal characteristics for adoptive cell therapy. J. Immunother. 31:8 (2008), 742–751.
330. Tran, E., et al. Cancer immunotherapy based on mutation-specific CD4+ T cells in a patient with epithelial cancer. Science 344:6184 (2014), 641–645.
331. Tsung, K., Norton, J.A., Lessons from coley's toxin. Surg. Oncol. 15:1 (2006), 25–28.
332. Tumeh, P.C., et al. PD-1 blockade induces responses by inhibiting adaptive immune resistance. Nature 515:7528 (2014), 568–571.
333. Turcotte, S., et al. Phenotype and function of T cells infiltrating visceral metastases from gastrointestinal cancers and melanoma: implications for adoptive cell transfer therapy. J. Immunol. 191:5 (2013), 2217–2225.
334. Urteaga, O., Pack, G.T., On the antiquity of melanoma. Cancer 19:5 (1966), 607–610.
335. Uyttenhove, C., et al. Evidence for a tumoral immune resistance mechanism based on tryptophan degradation by indoleamine 2,3-dioxygenase. Nat. Med. 9:10 (2003), 1269–1274.
336. Vanneman, M., Dranoff, G., Combining immunotherapy and targeted therapies in cancer treatment. Nat. Rev. Cancer 12:4 (2012), 237–251.
337. Vieweg, J., et al. Reversal of tumor-mediated immunosuppression. Clin. Cancer Res. 13:2 Pt 2 (2007), 727s–732s.
338. Viguier, M., et al. Foxp3 expressing CD4 + CD25(high) regulatory T cells are overrepresented in human metastatic melanoma lymph nodes and inhibit the function of infiltrating T cells. J. Immunol. 173:2 (2004), 1444–1453.
339. Vongtama, R., et al. Efficacy of radiation therapy in the local control of desmoplastic malignant melanoma. Head Neck 25:6 (2003), 423–428.
340. Wang, T.S., et al. Complete spontaneous regression of pulmonary metastatic melanoma. Dermatol. Surg. 24:8 (1998), 915–919.
341. Watson, J., Mochizuki, D., Interleukin 2: a class of T cell growth factors. Immunol. Rev. 51 (1980), 257–278.
342. Watson, J., Mochizuki, D., Gillis, S., T-cell growth factors: interleukin 2. Immunol. Today 1:6 (1980), 113–117.
343. Wei, M.C., et al. Proapoptotic BAX and BAK: a requisite gateway to mitochondrial dysfunction and death. Science 292:5517 (2001), 727–730.
344. Weide, B., et al. Myeloid-derived suppressor cells predict survival of patients with advanced melanoma: comparison with regulatory T cells and NY-ESO-1- or melan-A-specific T cells. Clin. Cancer Res. 20:6 (2014), 1601–1609.
345. Weinlich, G., et al. Decreased serum tryptophan concentration predicts poor prognosis in malignant melanoma patients. Dermatology 214:1 (2007), 8–14.
346. Wiemann, B., Starnes, C.O., Coley's toxins, tumor necrosis factor and cancer research: a historical perspective. Pharmacol. Ther. 64:3 (1994), 529–564.
347. Wolchok, J.D., et al. Guidelines for the evaluation of immune therapy activity in solid tumors: immune-related response criteria. Clin. Cancer Res. 15:23 (2009), 7412–7420.
348. Wolchok, J.D., et al. Four-year survival rates for patients with metastatic melanoma who received ipilimumab in phase II clinical trials. Ann. Oncol. 24:8 (2013), 2174–2180.
349. Wolchok, J.D., et al. Nivolumab plus ipilimumab in advanced melanoma. N. Engl. J. Med. 369:2 (2013), 122–133.
350. Wolfel, T., et al. A p16INK4a-insensitive CDK4 mutant targeted by cytolytic T lymphocytes in a human melanoma. Science 269:5228 (1995), 1281–1284.
351. Wolkers, M.C., et al. Redundancy of direct priming and cross-priming in tumor-specific CD8+ T cell responses. J. Immunol. 167:7 (2001), 3577–3584.
352. Woo, S.R., et al. Immune inhibitory molecules LAG-3 and PD-1 synergistically regulate T-cell function to promote tumoral immune escape. Cancer Res. 72:4 (2012), 917–927.
353. Woo, S.R., et al. STING-dependent cytosolic DNA sensing mediates innate immune recognition of immunogenic tumors. Immunity 41:5 (2014), 830–842.
354. Wyluda, E., et al. Durable complete responses off all treatment in patients with widely metastatic melanoma after sequential immunotherapy followed by a finte course of BRAF inhibitor therapy. Cancer Biol. Ther., 2015 ()submitted for publication.
355. Yao, X., et al. Levels of peripheral CD4(+)FoxP3(+) regulatory T cells are negatively associated with clinical response to adoptive immunotherapy of human cancer. Blood 119:24 (2012), 5688–5696.
356. Zhang, B., et al. Induced sensitization of tumor stroma leads to eradication of established cancer by T cells. J. Exp. Med. 204:1 (2007), 49–55.
357. Zhu, C., et al. The Tim-3 ligand galectin-9 negatively regulates T helper type 1 immunity. Nat. Immunol. 6:12 (2005), 1245–1252.
358. Zitvogel, L., et al. The anticancer immune response: indispensable for therapeutic success?. J. Clin. Invest. 118:6 (2008), 1991–2001.
359. de Vries, I.J., et al. Frequency of circulating Tregs with demethylated FOXP3 intron 1 in melanoma patients receiving tumor vaccines and potentially Treg-depleting agents. Clin. Cancer Res. 17:4 (2011), 841–848.
360. deLeeuw, R.J., et al. The prognostic value of FoxP3+ tumor-infiltrating lymphocytes in cancer: a critical review of the literature. Clin. Cancer Res. 18:11 (2012), 3022–3029.
361. Kaufman, H.L., Wolchok, J.D., Is tumor immunity the same thing as autoimmunity? Implications for cancer immunotherapy. J. Clin. Oncol., 2006, 2230–2232 (United States).