Immune-related biomarkers for diagnosis/prognosis and therapy monitoring of cutaneous melanoma

Expert Review of Molecular Diagnostics

Volumn 10, Issue 7, 2010, Pages 897-919

  Neagu, Monica ^a   Constantin, Carolina ^a   Tanase, Cristiana ^a  

^a VICTOR BABES NATIONAL INSTITUTE OF PATHOLOGY   (Romania)

Author keywords

cutaneous melanoma; diagnosis; immune markers; prognosis; therapy monitoring

Indexed keywords

ALPHA INTERFERON; ALPHA2A INTERFERON; ALPHA2B INTERFERON; BIOLOGICAL MARKER; CHEMOKINE RECEPTOR; CYTOKINE; CYTOTOXIC T LYMPHOCYTE ANTIGEN 4; CYTOTOXIC T LYMPHOCYTE ANTIGEN 4 ANTIBODY; DACARBAZINE; INTERLEUKIN 12; INTERLEUKIN 21; LACTATE DEHYDROGENASE; MELAN A; MELANOMA VACCINE; OLIGODEOXYNUCLEOTIDE; PEPTIDE VACCINE; PROTEIN S 100; RETINOIC ACID; SORAFENIB; TOLL LIKE RECEPTOR AGONIST; TUMOR CELL VACCINE; TUMOR MARKER;

ANTINEOPLASTIC ACTIVITY; CANCER CELL; CARCINOGENESIS; CELL INFILTRATION; CELL TYPE; CUTANEOUS MELANOMA; DENDRITIC CELL; GENETIC MARKER; HUMAN; IMMUNE DYSREGULATION; IMMUNE SYSTEM; IMMUNOCOMPETENT CELL; IMMUNOMODULATION; IMMUNOSUPPRESSIVE TREATMENT; IMMUNOTHERAPY; MAST CELL; MEMORY T LYMPHOCYTE; METASTASIS; MOLECULAR DIAGNOSIS; NATURAL KILLER CELL; PATIENT MONITORING; PROGNOSIS; REGULATORY T LYMPHOCYTE; REVIEW; SENTINEL LYMPH NODE; SIGNAL TRANSDUCTION; STEM CELL; UNSPECIFIED SIDE EFFECT; BASAL CELL CARCINOMA; BLOOD; CANCER STEM CELL; IMMUNOLOGY; MELANOMA; METABOLISM; METHODOLOGY; SKIN TUMOR;

CARCINOMA, BASAL CELL; DENDRITIC CELLS; GENETIC MARKERS; HUMANS; IMMUNOTHERAPY; KILLER CELLS, NATURAL; MELANOMA; NEOPLASTIC STEM CELLS; PROGNOSIS; SIGNAL TRANSDUCTION; SKIN NEOPLASMS; T-LYMPHOCYTES, REGULATORY; TUMOR MARKERS, BIOLOGICAL;

EID: 79952201673     PISSN: 14737159     EISSN: 17448352     Source Type: Journal    
DOI: 10.1586/erm.10.81     Document Type: Review

References (182)

1. Kalialis LV, Drzewiecki KT, Klyver H. Spontaneous regression of metastases from melanoma: review of the literature. Melanoma Res. 5, 275-282 (2009).
2. Rigel DS. Trends in dermatology: melanoma incidence. Arch. Dermatol. 146(3), 318 (2010).
3. Bos JD. Skin Immune System: Cutaneous Immunology and Clinical Immunodermatology (3rd Edition). CRC Press, NY, USA, 3-13 (2005).
4. Woods GM, Malley RC, Muller HK. The skin immune system and the challenge of tumor immunosurveillance. Eur. J. Dermatol. 15(2), 63-69 (2005). (Pubitemid 40434626)
5. Rabinovich GA, Gabrilovich D, Sotomayor EM. Immunosuppressive strategies that are mediated by tumor cells. Annu. Rev. Immunol. 25, 267-296 (2007). (Pubitemid 46697910)
6. Reiman JM, Kmieciak M, Manjili MH, Knutson KL. Tumor immunoediting and immunosculpting pathways to cancer progression. Semin. Cancer Biol. 17(4), 275-287 (2007). (Pubitemid 47211962)
7. Zattra E, Fortina AB, Bordignon M, Piaserico S, Alaibac M. Immunosuppression and melanocyte proliferation. Melanoma Res. 19(2), 63-68 (2009).
8. Gajewski TF. Failure at the effector phase: immune barriers at the level of the melanoma tumor microenvironment. Clin. Cancer Res. 13(18 Pt 1), 5256-5261 (2007). (Pubitemid 47510348)
9. Wang E, Marincola FM. cDNA arrays and the enigma of melanoma immune responsiveness. Cancer J. 7(1), 16-24 (2001). (Pubitemid 33759087)
10. Ilkovitch D, Lopez DM. Immune modulation by melanoma-derived factors. Exp. Dermatol. 17(12), 977-985 (2008).
11. Loser K, Brzoska T, Oji V et al. The neuropeptide a-melanocyte- stimulating hormone is critically involved in the development of cytotoxic CD8+ T cells in mice and humans. PLoS ONE 5(2), e8958 (2010).
12. Gould Rothberg BE, Bracken MB, Rimm DL. Tissue biomarkers for prognosis in cutaneous melanoma: a systematic review and meta-analysis. J. Natl Cancer Inst. 101(7), 452-474 (2009).
13. Staquicini FI, Tandle A, Libutti SK et al. A subset of host B-lymphocytes control melanoma metastasis through a MCAM/MUC18-dependent interaction: evidence from mice and humans. Cancer Res. 68(20), 8419-8428 (2008).
14. Egeblad M, Werb Z. New functions for the matrix metalloproteinases in cancer progression. Nat. Rev. Cancer 2, 161-174 (2002). (Pubitemid 37328786)
15. Väisänen AH, Kallioinen M, Turpeenniemi-Hujanen T. Comparison of the prognostic value of matrix metalloproteinases 2 and 9 in cutaneous melanoma. Hum. Pathol. 39(3), 377-385 (2008).
16. Hillen F, van de Winkel A, Creytens D, Vermeulen AH, Griffioen AW. Proliferating endothelial cells, but not microvessel density, are a prognostic parameter in human cutaneous melanoma. Melanoma Res. 16(5), 453-457 (2006). (Pubitemid 44511226)
17. Ohsie SJ, Sarantopoulos GP, Cochran AJ, Binder SW. Immunohistochemical characteristics of melanoma. J. Cutan. Pathol. 35(5), 433-444 (2008). (Pubitemid 351519417)
18. Smalley KS, Contractor R, Haass NK et al. Ki67 expression levels are a better marker of reduced melanoma growth following MEK inhibitor treatment than phospho-ERK levels. Br. J. Cancer 96(3), 445-449 (2007). (Pubitemid 46215215)
19. Alonso SR, Ortiz P, Polla'n M et al. Progression in cutaneous malignant melanoma is associated with distinct expression profiles-a tissue microarraybased study. Am. J. Pathol. 164(1), 193-203 (2004). (Pubitemid 38364604)
20. Hilliard NJ, Krahl D, Sellheyer K. p16 expression differentiates between desmoplastic Spitz nevus and desmoplastic melanoma. J. Cutan. Pathol. 36(7), 753-759 (2009).
21. Sanki A, Li W, Colman M, Karim RZ, Thompson JF, Scolyer RA. Reduced expression of p16 and p27 is correlated with tumour progression in cutaneous melanoma. Pathology 39(6), 551-557 (2007). (Pubitemid 350135628)
22. Mihic-Probst D, Kuster A, Kilgus S et al. Consistent expression of the stem cell renewal factor BMI-1 in primary and metastatic melanoma. Int. J. Cancer 121(8), 1764-1770 (2007). (Pubitemid 47417295)
23. Ladányi A. [Function and prognostic significance of immune cells infiltrating human tumors]. Magy Onkol. 48(1), 49-56 (2004).
24. Ladányi A, Mohos A, Somlai B et al. FOXP3+ cell density in primary tumor has no prognostic impact in patients with cutaneous malignant melanoma. Pathol. Oncol. Res. 16(3), 303-309 (2010).
25. Kiss J, Tímár J, Somlai B et al. Association of microvessel density with infiltrating cells in human cutaneous malignant melanoma. Pathol. Oncol. Res. 13(1), 21-31 (2007). (Pubitemid 46883543)
26. Ribas A, Kirkwood JM, Atkins MB et al. Phase I/II open-label study of the biologic effects of the interleukin-2 immunocytokine EMD 273063 (hu14.18-IL2) in patients with metastatic malignant melanoma. J. Transl. Med. 7, 68 (2009).
27. Zhao F, Falk C, Osen W, Kato M, Schadendorf D, Umansky V. Activation of p38 mitogen-activated protein kinase drives dendritic cells to become tolerogenic in ret transgenic mice spontaneously developing melanoma. Clin. Cancer Res. 15(13), 4382-4390 (2009).
28. Lee TH, Cho YH, Lee JD, Yang WI, Shin JL, Lee MG. Enhanced antitumor effect of dendritic cell based immunotherapy after intratumoral injection of radionuclide Ho-166 against B16 melanoma. Immunol. Lett. 106(1), 19-26 (2006). (Pubitemid 44093047)
29. Costache M, Simionescu O, Sajin M et al. Apoptosis in cutaneous melanomas. Rom. J. Morphol. Embryol. 48(4), 343-347 (2007).
30. Simionescu O, Dumitrescu D, Costache M, Blum A. Dermatoscopy of an invasive melanoma on the upper lip shows possible association with Laugier-Hunziker syndrome. J. Am. Acad. Dermatol. 59(5), 105-108 (2008).
31. Ladányi A, Kiss J, Somlai B et al. Density of DC-LAMP+ mature dendritic cells in combination with activated T lymphocytes infiltrating primary cutaneous melanoma is a strong independent prognostic factor. Cancer Immunol. Immunother. 56(9), 1459-1469 (2007). (Pubitemid 47024707)
32. Breslow A. Thickness, cross-sectional areas, and depth of invasion in the prognosis of cutaneous melanoma. Ann. Surg. 172, 902-908 (1970).
33. Anger M, Friedhofer H, Fukutaki MF, Ferreira MC, Landman G. Primary cutaneous melanoma: an 18-year study. Clinics (Sao Paulo) 65(3), 257-263 (2010).
34. Balch CM, Soong SJ, Gershenwald JE et al. Prognostic factors analysis of 17,600 melanoma patients: validation of the American Joint Committee on Cancer melanoma staging system. J. Clin. Oncol. 19(16), 3622-3634 (2001). (Pubitemid 32786275)
35. Donga C and Robertson GP. Immunoediting of leukocyte functions within the tumor microenvironment promotes cancer metastasis development. Biorheology 46(4), 265-279 (2009).
36. Degenhardt Y, Huang J, Greshock J et al. Distinct MHC gene expression patterns during progression of melanoma. Genes Chromosomes Cancer 49(2), 144-154 (2010).
37. Dissemond J, Kothen T, Mörs J et al. Downregulation of tapasin expression in progressive human malignant melanoma. Arch. Dermatol. Res. 295(2), 43-49 (2003). (Pubitemid 36791722)
38. Martins I, Sylla K, Deshayes F et al. Coexpression of major histocompatibility complex class II with chemokines and nuclear NFkB p50 in melanoma: a rational for their association with poor prognosis. Melanoma Res. 19(4), 226-237 (2009).
39. Quereux G, Pandolfino MC, Knol AC et al. Tissue prognostic markers for adoptive immunotherapy in melanoma. Eur. J. Dermatol. 17(4), 295-301 (2007). (Pubitemid 47051543)
40. Fecker LF, Geilen CC, Tchernev G et al. Loss of proapoptotic bcl-2-related multidomain proteins in primary melanomas is associated with poor prognosis. J. Invest. Dermatol. 126, 1366-1371 (2006). (Pubitemid 43997920)
41. Ständer S, Schwarz T. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is expressed in normal skin and cutaneous inflammatory diseases, but not in chronically UV-exposed skin and non-melanoma skin cancer. Am. J. Dermatopathol. 27(2), 116-121 (2005). (Pubitemid 40471096)
42. Nguyen T, Thomas W, Zhang XD, Gray C, Hersey P. Immunologicallymediated tumor cell apoptosis: the role of TRAIL in T cell and cytokine-mediated responses to melanoma. Forum (Genova) 10(3), 243-252 (2000). (Pubitemid 32060873)
43. Wu JJ, Zhang XD, Gillespie S, Hersey P. Selection for TRAIL resistance results in melanoma cells with high proliferative potential. FEBS Lett. 579(9), 1940-1944 (2005). (Pubitemid 40404035)
44. Zhuang L, Lee CS, Scolyer RA et al. Progression in melanoma is associated with decreased expression of death receptors for tumor necrosis factor-related apoptosisinducing ligand. Hum. Pathol. 37(10), 1286-1294 (2006). (Pubitemid 44380273)
45. Bron LP, Scolyer RA, Thompson JF, Hersey P. Histological expression of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in human primary melanoma. Pathology 36(6), 561-565 (2004). (Pubitemid 40091467)
46. Logozzi M, De Milito A, Lugini L et al. High levels of exosomes expressing CD63 and caveolin-1 in plasma of melanoma patients. PLoS ONE 4(4), e5219 (2009).
47. Lewis TB, Robison JE, Bastien R et al. Molecular classification of melanoma using real-time quantitative reverse transcriptasepolymerase chain reaction. Cancer 104(8), 1678-1686 (2005). (Pubitemid 41437431)
48. García-Gutiérrez M, Toussaint-Caire S, González- Sánchez P, Ortiz-Hidalgo C. Multiple desmoplastic cellular neurothekeomas localized to the face of a 16-year-old boy. Am. J. Dermatopathol. 32(5), 509-513 (2010).
49. Kazakov DV, Kutzner H, Rütten A et al. The anti-MAGE antibody B57 as a diagnostic marker in melanocytic lesions. Am. J. Dermatopathol. 26(2), 102-107 (2004). (Pubitemid 38429057)
50. Zhu X, Asa SL, Ezzat S. Genetic and epigenetic mechanisms down-regulate FGF receptor 2 to induce melanoma-associated antigen A in breast cancer. Am. J. Pathol. 176(5), 2333-2343 (2010).
51. Zhang S, Zhou X, Yu H, Yu Y. Expression of tumor-specific antigen MAGE, GAGE and BAGE in ovarian cancer tissues and cell lines. BMC Cancer 10, 163 (2010).
52. Paul AK, Ciesielski MJ, Sajjad M et al. Expression of HMP/AN2, a melanoma associated antigen, in murine cerebral gliomas: potential for radioimmunotargeting. J. Neurooncol. 94, 21-30 (2009).
53. Liu F, Killian JK, Yang M et al. Epigenomic alterations and gene expression profiles in respiratory epithelia exposed to cigarette smoke condensate. Oncogene 29(25), 3650-3664 (2010).
54. Vourc'h-Jourdain M, Volteau C, Nguyen JM, Khammari A, Dreno B. Melanoma gene expression and clinical course. Arch. Dermatol. Res. 301(9), 673-679 (2009).
55. Neagu M, Constantin C, Manda G, Margaritescu I. Biomarkers of metastatic melanoma. Biomarkers Med. 3(1), 71-89 (2009).
56. Ménard C, Ghiringhelli F, Roux S et al. CTLA-4 blockade confers lymphocyte resistance to regulatory T-cells in advanced melanoma: surrogate marker of efficacy of tremelimumab? Clin. Cancer Res. 14(16), 5242-5249 (2008).
57. Hernberg M, Mattila PS, Rissanen M et al. The prognostic role of blood lymphocyte subset distribution in patients with resected high-risk primary or regionally metastatic melanoma. J. Immunother. 30(7), 773-779 (2007). (Pubitemid 47480760)
58. Casado JG, Soto R, DelaRosa O et al. CD8 T cells expressing NK associated receptors are increased in melanoma patients and display an effector phenotype. Cancer Immunol. Immunother. 54(12), 1162-1171 (2005). (Pubitemid 41416948)
59. Campillo JA, Martínez-Escribano JA, Moya-Quiles MR et al. Natural killer receptors on CD8 T cells and natural killer cells from different HLA-C phenotypes in melanoma patients. Clin. Cancer Res. 12(16), 4822-4831 (2006). (Pubitemid 44338566)
60. Avogadri F, Yuan J, Yang A, Schaer D, Wolchok JD. Modulation of CTLA-4 and GITR for cancer immunotherapy. Curr. Top. Microbiol. Immunol. DOI: 10.1007/82-2010-49 (2010) (Epub ahead of print).
61. Sakaguchi S. Naturally arising CD4+ regulatory T cells for immunologic self-tolerance and negative control of immune responses. Annu. Rev. Immunol. 22, 531-562 (2004). (Pubitemid 38680433)
62. Fehérvari Z, Sakaguchi S. CD4+ Tregs and immune control. J. Clin. Invest. 114(9), 1209-1217 (2004).
63. Baumgartner J, Wilson C, Palmer B, Richter D, Banerjee A, McCarter M. Melanoma induces immunosuppression by up-regulating FOXP3+ regulatory T cells. J. Surg. Res. 141(1), 72-77 (2007). (Pubitemid 46898447)
64. Clark RA, Kupper TS. IL-15 and dermal fibroblasts induce proliferation of natural regulatory T cells isolated from human skin. Blood 109(1), 194-202 (2007). (Pubitemid 46053061)
65. Vence L, Palucka AK, Fay JW et al. Circulating tumor antigen-specific regulatory T cells in patients with metastatic melanoma. Proc. Natl Acad. Sci. USA 18(2), 59-70 (2007).
66. McCarter MD, Baumgartner J, Escobar GA et al. Immunosuppressive dendritic and regulatory T cells are upregulated in melanoma patients. Ann. Surg. Oncol. 14(10), 2854-2860 (2007). (Pubitemid 47460650)
67. Cesana GC, DeRaffele G, Cohen S et al. Characterization of CD4+CD25+ regulatory T cells in patients treated with high-dose interleukin-2 for metastatic melanoma or renal cell carcinoma. J. Clin. Oncol. 24(7), 1169-1177 (2006). (Pubitemid 46638815)
68. Sutmuller RP, van Duivenvoorde LM, van Elsas A et al. Synergism of cytotoxic T lymphocyte-associated antigen 4 blockade and depletion of CD25+ regulatory T cells in antitumor therapy reveals alternative pathways for suppression of autoreactive cytotoxic T lymphocyte responses. J. Exp. Med. 194(6), 823-832 (2001). (Pubitemid 32983017)
69. Nakai N, Katoh N, Kitagawa T, Ueda E, Takenaka H, Kishimoto S. Immunoregulatory T cells in the peripheral blood of melanoma patients treated with melanoma antigen-pulsed mature monocyte-derived dendritic cell vaccination. J. Dermatol. Sci. 54(1), 31-37 (2009).
70. Stockis J, Fink W, François V et al. Comparison of stable human Treg and Th clones by transcriptional profiling. Eur. J. Immunol. 39(3), 869-882 (2009).
71. Ghiringhelli F, Ménard C, Terme M et al. CD4+CD25+ regulatory T cells inhibit natural killer cell functions in a transforming growth factor-b-dependent manner. J. Exp. Med. 202(8), 1075-1085 (2005). (Pubitemid 41464501)
72. Konjevic G, Mirjacic Martinovic K, Jurisic V, Babovic N, Spuzic I. Biomarkers of suppressed natural killer (NK) cell function in metastatic melanoma: decreased NKG2D and increased CD158a receptors on CD3-CD16+ NK cells. Biomarkers 14(4), 258-270 (2009).
73. Frederiksen KS, Lundsgaard D, Freeman JA et al. IL-21 induces in vivo immune activation of NK cells and CD8+ T cells in patients with metastatic melanoma and renal cell carcinoma. Cancer Immunol. Immunother. 57(10), 1439-1449 (2008).
74. Konjevic G, Jovic V, Vuletic A, Radulovic S, Jelic S, Spuzic I. CD69 on CD56+ NK cells and response to chemoimmunotherapy in metastatic melanoma. Eur. J. Clin. Invest. 37(11), 887-960 (2007).
75. Guillot B, Portalès P, Thanh AD et al. The expression of cytotoxic mediators is altered in mononuclear cells of patients with melanoma and increased by interferon-a treatment. Br. J. Dermatol. 152(4), 690-696 (2005). (Pubitemid 40571301)
76. Debenedictis C, Joubeh S, Zhang G, Barria M, Ghohestani RF. Immune functions of the skin. Clin. Dermatol. 19, 573-585 (2001). (Pubitemid 32927173)
77. Baumgartner JM, Gonzalez R, Lewis KD et al. Increased survival from stage IV melanoma associated with fewer regulatory T cells. J. Surg. Res. 154(1), 13-20 (2009).
78. Charles J, Di Domizio J, Salameire D et al. Characterization of circulating dendritic cells in melanoma: role of CCR6 in plasmacytoid dendritic cell recruitment to the tumor. J. Invest. Dermatol. 130(6), 1646-1656 (2010).
79. Sabatino M, Stroncek DF, Klein H, Marincola FM, Wang E. Stem cells in melanoma development. Cancer Lett. 279(2), 119-125 (2009).
80. La Porta C. Cancer stem cell: lessons from melanoma. Stem Cell Rev. Rep. 5, 61-65 (2009).
81. Deichmann M, Thome M, Egner U, Hartschuh W, Kurzen H. The chemoresistance gene ABCG2 (MXR/BCRP1/ABCP1) is not expressed in melanomas but in single neuroendocrine carcinomas of the skin. J. Cutan. Pathol. 32(7), 467-473 (2005). (Pubitemid 41039396)
82. Chen KG, Szakács G, Annereau JP et al. Principal expression of two mRNA isoforms (ABCB 5a and ABCB 5b) of the ATP-binding cassette transporter gene ABCB 5 in melanoma cells and melanocytes. Pigment Cell Res. 18(2), 102-112 (2005). (Pubitemid 40445046)
83. Schatton T, Murphy GF, Frank NY et al. Identification of cells initiating human melanomas. Nature 451(7176), 345-349 (2008).
84. Schatton T, Schütte U, Frank NY et al. Modulation of T-cell activation by malignant melanoma initiating cells. Cancer Res. 70(2), 697-708 (2010).
85. Fusi A, Ochsenreither S, Busse A, Rietz A, Keilholz U. Expression of the stem cell marker nestin in peripheral blood of patients with melanoma. Br. J. Dermatol. 163(1), 107-114 (2010).
86. Lugovic L, Situm M, Buljan M, Poduje S, Sebetic K. Results of the determination of serum markers in patients with malignant melanoma. Coll. Antropol. 31(Suppl. 1), 7-11 (2007).
87. Garnier JP, Letellier S, Cassinat B et al. Clinical value of combined determination of plasma L-DOPA/tyrosine ratio, S100B, MIA and LDH in melanoma. Eur. J. Cancer 43(4), 816-821 (2007). (Pubitemid 46502913)
88. Faries MB, Gupta RK, Ye X et al. A comparison of 3 tumor markers (MIA, TA90IC, S100B) in stage III melanoma patients. Cancer Invest. 25(5), 285-293 (2007). (Pubitemid 47185072)
89. Soubrane C, Rixe O, Meric JB, Khayat D, Mouawad R. Pretreatment serum interleukin-6 concentration as a prognostic factor of overall survival in metastatic malignant melanoma patients treated with biochemotherapy: a retrospective study. Melanoma Res. 15(3), 199-204 (2005). (Pubitemid 40839468)
90. Tas F, Oguz H, Argon A et al. The value of serum levels of IL-6, TNF-a, and erythropoietin in metastatic malignant melanoma: serum IL-6 level is a valuable prognostic factor at least as serum LDH in advanced melanoma. Med. Oncol. 22(3), 241-246 (2005). (Pubitemid 41176320)
91. Balch CM, Gershenwald JE, Soong S-J et al. Final version of 2009 AJCC melanoma staging and classification. J. Clin. Oncol. 27, 6199-6206 (2009).
92. Gupta RK, Cochran AJ, Hsueh EC, Trocha SD, Morton DL. Melanoma (Section 3L). In: Guidelines for the Use of Tumor Markers in Malignant Melanoma. National Academy of Clinical Biochemistry, Washington, DC, USA 1-42 (2005).
93. Botella-Estrada R, Escudero M, O'Connor JE et al. Cytokine production by peripheral lymphocytes in melanoma. Eur. Cytokine Netw. 16(1), 47-55 (2005). (Pubitemid 40478076)
94. Yurkovetsky ZR, Kirkwood JM, Edington HD et al. Multiplex analysis of serum cytokines in melanoma patients treated with interferon-a2b. Clin. Cancer Res. 13(8), 2422-2428 (2007). (Pubitemid 46698593)
95. Schwinn N, Vokhminova D, Sucker A et al. Interferon-g down-regulates NKG2D ligand expression and impairs the NKG2D-mediated cytolysis of MHC class I-deficient melanoma by natural killer cells. Int. J. Cancer 124(7), 1594-1604 (2009).
96. Paschen A, Sucker A, Hill B et al. Differential clinical significance of individual NKG2D ligands in melanoma: soluble ULBP2 as an indicator of poor prognosis superior to S100B. Clin. Cancer Res. 15(16), 5208-5215 (2009).
97. Andrés R, Mayordomo JI, Visus C et al. Prognostic significance and diagnostic value of protein S-100 and tyrosinase in patients with malignant melanoma. Am. J. Clin. Oncol. 31(4), 335-339 (2008).
98. Smit LH, Korse CM, Hart AA et al. Normal values of serum S-100B predict prolonged survival for stage IV melanoma patients. Eur. J. Cancer 41(3), 386-392 (2005). (Pubitemid 40187209)
99. Dumitrascu G, Constantin C, Manda G et al. Serum markers in skin melanoma-preliminary study. Roum. Arch. Microbiol. Immunol. 69, 41-51 (2009).
100. Hoek K, Rimm DL, Williams KR et al. Expression profiling reveals novel pathways in the transformation of melanocytes to melanomas. Cancer Res. 64(15), 5270-5282 (2004). (Pubitemid 39006547)
101. Pinnix CC, Lee JT, Liu ZJ et al. Active Notch1 confers a transformed phenotype to primary human melanocytes. Cancer Res. 69(13), 5312-5320 (2009).
102. Kang S, Yang C, Luo R. Induction of CCL2 by siMAML1 through upregulation of TweakR in melanoma cells. Biochem. Biophys. Res. Commun. 372(4), 629-633 (2008).
103. Critchley-Thorne RJ, Yan N, Nacu S, Weber J, Holmes SP, Lee PP. Downregulation of the interferon signaling pathway in T lymphocytes from patients with metastatic melanoma. PLoS Med. 4(5), e176 (2007).
104. Wang W, Edington HD, Rao UN et al. Modulation of signal transducers and activators of transcription 1 and 3 signaling in melanoma by high-dose IFNa2b. Clin. Cancer Res. 13(5), 1523-1531 (2007). (Pubitemid 46450444)
105. Varker KA, Kondadasula SV, Go MR et al. Multiparametric flow cytometric analysis of signal transducer and activator of transcription 5 phosphorylation in immune cell subsets in vitro and following interleukin-2 immunotherapy. Clin. Cancer Res. 12(19), 5850-5858 (2006). (Pubitemid 44629618)
106. Zhao F, Falk C, Osen W, Kato M, Schadendorf D, Umansky V. Activation of p38 mitogen-activated protein kinase drives dendritic cells to become tolerogenic in ret transgenic mice spontaneously developing melanoma. Clin. Cancer Res. 15(13), 4382-4390 (2009).
107. Tanase Pistol C, Neagu M, Albulescu R. Key signaling molecules in pituitary tumors. Expert Rev. Mol. Diagn. 9(8), 859-877 (2009).
108. Chien AJ, Moore EC, Lonsdorf AS et al. Activated Wnt/b-catenin signaling in melanoma is associated with decreased proliferation in patient tumors and a murine melanoma model. Proc. Natl Acad. Sci. USA 106(4), 1193-1198 (2009).
109. Arenberger P, Arenbergerova M, Vohradnikova O, Kremen J. Early detection of melanoma progression by quantitative real-time RT-PCR analysis for multiple melanoma markers. Keio J. Med. 57(1), 57-64 (2008). (Pubitemid 351744047)
110. Sharma B, Singh S, Varney ML, Singh RK. Targeting CXCR1/CXCR2 receptor antagonism in malignant melanoma. Expert Opin. Ther. Targets 14(4), 435-442 (2010).
111. Franco R, Cantile M, Scala S et al. Histomorphologic parameters and CXCR4 mRNA and protein expression in sentinel node melanoma metastasis are correlated to clinical outcome. Cancer Biol. Ther. 9(6), 423-429 (2010).
112. Sarff M, Edwards D, Dhungel B et al. OX40 (CD134) expression in sentinel lymph nodes correlates with prognostic features of primary melanomas. Am. J. Surg. 195(5), 621-625 (2008). (Pubitemid 351522206)
113. Brennecke S, Deichmann M, Naeher H, Kurzen H. Decline in angiogenic factors, such as interleukin-8, indicates response to chemotherapy of metastatic melanoma. Melanoma Res. 15(6), 515-522 (2005). (Pubitemid 44124263)
114. Varney ML, Johansson SL, Singh RK. Distinct expression of CXCL8 and its receptors CXCR1 and CXCR2 and their association with vessel density and aggressiveness in malignant melanoma. Am. J. Clin. Pathol. 125, 209-216 (2006). (Pubitemid 43167161)
115. Schutyser E, Su Y, Yu Y et al. Hypoxia enhances CXCR4 expression in human microvascular endothelial cells and human melanoma cells. Eur. Cytokine Netw. 18(2), 59-70 (2007). (Pubitemid 47262360)
116. Guidolin D, Crivellato E, Nico B, Andreis PG, Nussdorfer GG, Ribatti D. An image analysis of the spatial distribution of perivascular mast cells in human melanoma. Int. J. Mol. Med. 17(6), 981-987 (2006).
117. Ch'ng S, Wallis RA, Yuan L, Davis PF, Tan ST. Mast cells and cutaneous malignancies. Mod. Pathol. 19(1), 149-159 (2006). (Pubitemid 43250990)
118. Theoharides T, Conti P. Mast cells: the Jekyll and Hyde of tumor growth. Trends Immunol. 25, 235-241 (2004). (Pubitemid 38501669)
119. Lu C, Kerbel R. Interleukin-6 undergoes transition from a paracrine growth inhibitor to autocrine stimulator during human melanoma progression. J. Cell. Biol. 120, 1281-1288 (1993). (Pubitemid 23064182)
120. Redondo P. Update on melanoma: incidence, development and biological aspects. An. Sist. Sanit. Navar. 23(1), 67-84 (2000). (Pubitemid 30227931)
121. Viros A, Fridlyand J, Bauer J et al. Improving melanoma classification by integrating genetic and morphologic features. PLoS Med. 5(6), e120 (2008).
122. Ugurel S, Schrama D, Keller G et al. Impact of the CCR5 gene polymorphism on the survival of metastatic melanoma patients receiving immunotherapy. Cancer Immunol. Immunother. 57(5), 685-691 (2008). (Pubitemid 351641030)
123. Takata M, Murata H, Saida T. Molecular pathogenesis of malignant melanoma: a different perspective from the studies of melanocytic nevus and acral melanoma. Pigment Cell Melanoma Res. 23(1), 64-71 (2010).
124. Jonsson GB, Busch C, Knappskog S et al. Gene expression profiling-based identification of molecular subtypes in stage IV melanomas with different clinical outcome. Clin. Cancer Res. 16(13), 3356-3367 (2010).
125. Woodman SE, Trent JC, Stemke-Hale K et al. Activity of dasatinib against L576P KIT mutant melanoma: molecular, cellular, and clinical correlates. Mol. Cancer Ther. 8(8), 2079-2085 (2009).
126. Su DM, Zhang Q, Wang X et al. Two types of human malignant melanoma cell lines revealed by expression patterns of mitochondrial and survival-apoptosis genes: implications for malignant melanoma therapy. Mol. Cancer Ther. 8(5), OF1-OF13 (2009).
127. Lalou C, Scamuffa N, Mourah S et al. Inhibition of the proprotein convertases represses the invasiveness of human primary melanoma cells with altered p53, CDKN2A and N-Ras genes. PLoS ONE 5(4), e9992 (2010).
128. Zhang H, Sun XF, Synnerstad I, Rosdahl I. Importance of FAS-1377, FAS-670, and FASL-844 polymorphisms in tumor onset, progression, and pigment phenotypes of Swedish patients with melanoma: a case-control analysis. Cancer J. 13(4), 233-237 (2007).
129. Philippidou D, Schmitt M, Moser D et al. Signatures of microRNAs and selected microRNA target genes in human melanoma. Cancer Res. 70(10), 4163-4173 (2010).
130. Segura MF, Belitskaya-Lévy I, Rose AE et al. Melanoma microRNA signature predicts post-recurrence survival. Clin. Cancer Res. 16(5), 1577-1586 (2010).
131. Ribas A. Update on immunotherapy for melanoma J. Natl Compr. Canc. Netw. 4(7), 687-694 (2006).
132. Hsueh EC, Famatiga E, Shu S, Ye X, Morton DL. Peripheral blood CD4+ T-cell response before postoperative active immunotherapy correlates with clinical outcome in metastatic melanoma. Ann. Surg. Oncol. 11(10), 892-899 (2004). (Pubitemid 40486674)
133. Gajewski TF. Identifying and overcoming immune resistance mechanisms in the melanoma tumor microenvironment. Clin. Cancer Res. 12, 2326s-2330s (2006).
134. Schrama D, Hauschild A, Becker JC. Immunmodulatory antibodies in the treatment of skin cancer. Hautarzt 59(10), 806-813 (2008).
135. Wolchok JD, Saenger Y. The mechanism of anti-CTLA-4 activity and the negative regulation of T-cell activation. Oncologist 13(Suppl. 4), 2-9 (2008).
136. Langer LF, Clay TM, Morse MA. Update on anti-CTLA-4 antibodies in clinical trials. Expert Opin. Biol. Ther. 7(8), 1245-1256 (2007). (Pubitemid 47305249)
137. Ribas A, Comin-Anduix B, Economou JS et al. Intratumoral immune cell infiltrates, FoxP3, and indoleamine 2,3-dioxygenase in patients with melanoma undergoing CTLA4 blockade. Clin. Cancer Res. 5(1), 390-399 (2009).
138. Munn DH, Shafizadeh E, Attwood J, Bondarev I, Pashine A, Mellor A. Inhibition of T cell proliferation by macrophage tryptophan catabolism. J. Exp. Med. 189, 1363-1372 (1999). (Pubitemid 29227522)
139. Kirkwood JM, Tarhini AA, Panelli MC et al. Next generation of immunotherapy for melanoma. J. Clin. Oncol. 26(20), 3445-3455 (2008).
140. Pashenkov M, Goëss G, Wagner CA et al. Phase II trial of a toll-like receptor 9-activating oligonucleotide in patients with metastatic melanoma. J. Clin. Oncol. 24(36), 5716-5724 (2006). (Pubitemid 46631314)
141. Dummer R, Hauschild A, Becker JC et al. An exploratory study of systemic administration of the toll-like receptor-7 agonist 852A in patients with refractory metastatic melanoma. Clin. Cancer Res. 14(3), 856-864 (2008). (Pubitemid 351231170)
142. Wolf IH, Kodama K, Cerroni L, Kerl H. Nature of inflammatory infiltrate in superficial cutaneous malignancies during topical imiquimod treatment. Am. J. Dermatopathol. 29(3), 237-241 (2007). (Pubitemid 46801921)
143. Delcayre A, Shu H, Le Pecq JB. Dendritic cell-derived exosomes in cancer immunotherapy: exploiting nature's antigen delivery pathway. Expert Rev. Anticancer Ther. 5(3), 537-547 (2005). (Pubitemid 40894984)
144. Hao S, Bai O, Yuan J, Qureshi M, Xiang J. Dendritic cell-derived exosomes stimulate stronger CD8+ CTL responses and antitumor immunity than tumor cellderived exosomes. Cell. Mol. Immunol. 3(3), 205-211 (2006).
145. Escudier B, Dorval T, Chaput N et al. Vaccination of metastatic melanoma patients with autologous dendritic cell (DC) derived-exosomes: results of the first Phase I clinical trial. J. Transl. Med. 3(1), 10. (2005).
146. Davis ID, Chen Q, Morris L et al. Blood dendritic cells generated with Flt3 ligand and CD40 ligand prime CD8+ T cells efficiently in cancer patients. J. Immunother. 29(5), 499-511 (2006). (Pubitemid 44395275)
147. Aarntzen EH, Figdor CG, Adema GJ, Punt CJ, de Vries IJ. Dendritic cell vaccination and immune monitoring. Cancer Immunol. Immunother. 57(10), 1559-1568 (2008).
148. Mayordomo JI, Andres R, Isla MD et al. Results of a pilot trial of immunotherapy with dendritic cells pulsed with autologous tumor lysates in patients with advanced cancer. Tumori 93(1), 26-30 (2007). (Pubitemid 46506526)
149. Nakai N, Katoh N, Germeraad WT et al. Immunohistological analysis of peptideinduced delayed-type hypersensitivity in advanced melanoma patients treated with melanoma antigen-pulsed mature monocyte-derived dendritic cell vaccination. J. Dermatol. Sci. 53(1), 40-47 (2009).
150. van de Ven R, Lindenberg JJ, Oosterhoff D et al. Selective transduction of mature DC in human skin and lymph nodes by CD80/CD86-targeted fiber-modified adenovirus-5/3. J. Immunother. 32(9), 895-906 (2009).
151. Erdmann M, Schuler-Thurner B. Dendritic cell vaccines in metastasized malignant melanoma. G. Ital. Dermatol. Venereol. 143(4), 235-250 (2008).
152. Speiser DE, Pittet MJ, Rimoldi D, Guillaume P, Luescher IF, Liénard D et al. Evaluation of melanoma vaccines with molecularly defined
153. Chapman PB. Melanoma vaccines. Semin. Oncol. 34(6), 516-523 (2007). (Pubitemid 350236310)
154. Ralph SJ. An update on malignant melanoma vaccine research: insights into mechanisms for improving the design and potency of melanoma therapeutic vaccines. Am. J. Clin. Dermatol. 8(3), 123-141 (2007). (Pubitemid 46998541)
155. Slingluff CL Jr, Petroni GR, Olson W et al. Helper T-cell responses and clinical activity of a melanoma vaccine with multiple peptides from MAGE and melanocytic differentiation antigens. J. Clin. Oncol. 26(30), 4973-4980 (2008).
156. Lienard D, Avril MF, Le Gal FA et al. Vaccination of melanoma patients with Melan-A/Mart-1 peptide and Klebsiella outer membrane protein p40 as an adjuvant. J. Immunother. 32(8), 875-878 (2009).
157. Cesana GC, DeRaffele G, Cohen S et al. Characterization of CD4+CD25+ regulatory T cells in patients treated with high-dose interleukin-2 for metastatic melanoma or renal cell carcinoma. J. Clin. Oncol. 24(7), 1169-1177 (2006). (Pubitemid 46638815)
158. Andersen MH, Gehl J, Reker S et al. Dynamic changes of specific T cell responses to melanoma correlate with IL-2 administration. Semin. Cancer Biol. 13(6), 449-459 (2003). (Pubitemid 38156137)
159. Atkins MB. Cytokine-based therapy and biochemotherapy for advanced melanoma. Clin. Cancer Res. 12(7 Pt 2), 2353s-2358s (2006).
160. Varker KA, Kondadasula SV, Go MR et al. Multiparametric flow cytometric analysis of signal transducer and activator of transcription 5 phosphorylation in immune cell subsets in vitro and following interleukin-2 immunotherapy. Clin. Cancer Res. 12(19), 5850-5858 (2006). (Pubitemid 44629618)
161. Mackensen A, Meidenbauer N, Vogl S, Laumer M, Berger J, Andreesen R. Phase I study of adoptive T-cell therapy using antigen-specific CD8+ T cells for the treatment of patients with metastatic melanoma. J. Clin. Oncol. 24(31), 5060-5069 (2006). (Pubitemid 46631410)
162. Green DS, Dalgleish AG, Belonwu N, Fischer MD, Bodman-Smith MD. Topical imiquimod and intralesional interleukin-2 increase activated lymphocytes and restore the Th1/Th2 balance in patients with metastatic melanoma. Br. J. Dermatol. 159(3), 606-614 (2008).
163. Mortarini R, Vegetti C, Molla A et al. Impaired STAT phosphorylation in T cells from melanoma patients in response to IL-2: association with clinical stage. Clin. Cancer Res. 15(12), 4085-4094 (2009).
164. Gerlini G, Mariotti G, Chiarugi A et al. Induction of CD83+CD14+ nondendritic antigen-presenting cells by exposure of monocytes to IFN-a. J. Immunol. 181(5), 2999-3008 (2008).
165. Zimmerer JM, Lesinski GB, Ruppert AS et al. Gene expression profiling reveals similarities between the in vitro and in vivo responses of immune effector cells to IFN-a. Clin. Cancer Res. 14(18), 5900-5906 (2008).
166. Schmidt H, Bastholt L, Geertsen P et al. Elevated neutrophil and monocyte counts in peripheral blood are associated with poor survival in patients with metastatic melanoma: a prognostic model. Br. J. Cancer 93(3), 273-278 (2005). (Pubitemid 43080028)
167. Friebe A, Schwarz MJ, Schmid-Wendtner M et al. Pretreatment levels of sTNF-R1 and sIL-6R are associated with a higher vulnerability for IFN-a-induced depressive symptoms in patients with malignant melanoma. J. Immunother. 30(3), 333-337 (2007). (Pubitemid 46586649)
168. Escudier B, Lassau N, Angevin E et al. Phase I trial of sorafenib in combination with IFN a-2a in patients with unresectable and/or metastatic renal cell carcinoma or malignant melanoma. Clin. Cancer Res. 13(6), 1801-1809 (2007). (Pubitemid 46952949)
169. Ahmadzadeh M, Antony PA, Rosenberg SA. IL-2 and IL-15 each mediate de novo induction of FOXP3 expression in human tumor antigen-specific CD8 T cells. J. Immunother. 30(3), 294-302 (2007). (Pubitemid 46586645)
170. Cocco C, Pistoia V, Airoldi I. New perspectives for melanoma immunotherapy: role of IL-12. Curr. Mol. Med. 9(4), 459-469 (2009).
171. Sanchez-Perez L, Kottke T, Daniels GA et al. Killing of normal melanocytes, combined with heat shock protein 70 and CD40L expression, cures large established melanomas. J. Immunol. 177(6), 4168-4177 (2006). (Pubitemid 44359952)
172. Tanase-Pistol C, Raducan E, Dima SO et al. Assessment of soluble angiogenic markers in pancreatic cancer. Biomarkers Med. 2(5), 447-455 (2008).
173. Yang Y, Iyer LK, Adelstein SJ, Kassis AI. Integrative genomic data mining for discovery of potential blood-borne biomarkers for early diagnosis of cancer. PLoS ONE 3(11), e3661 (2008).
174. Weigel MT, Dowsett M. Current and emerging biomarkers in breast cancer: prognosis and prediction. Endocr. Relat. Cancer 17(4), R245-R262 (2010).
175. Roesch-Ely M, Leipold A, Nees M et al. Proteomic analysis of field cancerization in pharynx and oesophagus: a prospective pilot study. J. Pathol. 221(4), 462-470 (2010).
176. Jennings L, Murphy GM. Predicting outcome in melanoma: where are we now? Br. J. Dermatol. 161, 496-503 (2009).
177. Schiltz PM, Dillman RO. Serum cytokines in metastatic melanoma patients treated with an autologous tumor vaccine. Cancer Biother. Radiopharm. 18(6), 879-886 (2003). (Pubitemid 38064018)
178. Mian S, Ugurel S, Parkinson E et al. Serum proteomic fingerprinting discriminates between clinical stages and predicts disease progression in melanoma patients. J. Clin. Oncol. 23(22), 5088-5093 (2005). (Pubitemid 46224016)
179. Hofmann MA, Gussmann F, Fritsche A et al. Diagnostic value of melanoma inhibitory activity serum marker in the follow-up of patients with stage I or II cutaneous melanoma. Melanoma Res. 19(1), 17-23 (2009).
180. O'Day SJ, Maio M, Chiarion-Sileni V et al. Efficacy and safety of ipilimumab monotherapy in patients with pretreated advanced melanoma: a multicenter single-arm Phase II study. Ann. Oncol. 21(8), 1712-1717 (2010).
181. Adamina M, Weber WP, Rosenthal R et al. Heterologous prime-boost immunotherapy of melanoma patients with influenza virosomes, and recombinant vaccinia virus encoding 5 melanoma epitopes and 3 co-stimulatory molecules. A multi-centre Phase I/II open labeled clinical trial. Contemp. Clin. Trials 29(2), 165-181 (2008). (Pubitemid 351255516)
182. Jilaveanu LB, Aziz SA, Kluger HM. Chemotherapy and biologic therapies for melanoma: do they work? Clin. Dermatol. 27(6), 614-625 (2009).