Tapping CD4 T cells for cancer immunotherapy: The choice of personalized genomics

Journal of Immunology

Volumn 194, Issue 5, 2015, Pages 2049-2056

  Zanetti, Maurizio ^a  

^a UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIGEN; MAF NEOANTIGEN; TUMOR ANTIGEN; UNCLASSIFIED DRUG; CANCER VACCINE; ERBB2IP PROTEIN, HUMAN; SIGNAL TRANSDUCING ADAPTOR PROTEIN;

ANTIBODY RESPONSE; ANTIGEN RECOGNITION; ARTICLE; CANCER IMMUNOTHERAPY; CANCER PREVENTION; CD4+ T LYMPHOCYTE; DRUG APPROVAL; FOOD AND DRUG ADMINISTRATION; GENE PRODUCT; GENOMICS; HELPER CELL; HUMAN; IMMUNOLOGICAL TOLERANCE; NONHUMAN; PERSONALIZED MEDICINE; PRIORITY JOURNAL; TUMOR IMMUNITY; ANIMAL; BILE DUCT NEOPLASMS; CHOLANGIOCARCINOMA; GENE EXPRESSION; GENETICS; IMMUNOLOGY; IMMUNOTHERAPY; INTRAHEPATIC BILE DUCT; METASTASIS; MUTATION; PATHOLOGY;

ADAPTOR PROTEINS, SIGNAL TRANSDUCING; ANIMALS; ANTIGENS, NEOPLASM; BILE DUCT NEOPLASMS; BILE DUCTS, INTRAHEPATIC; CANCER VACCINES; CD4-POSITIVE T-LYMPHOCYTES; CHOLANGIOCARCINOMA; GENE EXPRESSION; GENOMICS; HUMANS; IMMUNOTHERAPY; INDIVIDUALIZED MEDICINE; MUTATION; NEOPLASM METASTASIS;

EID: 84924370556     PISSN: 00221767     EISSN: 15506606     Source Type: Journal    
DOI: 10.4049/jimmunol.1402669     Document Type: Article

References (155)

1. Waldmann, T. A. 2003. Immunotherapy: past, present and future. Nat. Med. 9: 269-277.
2. Baeuerle, P. A., and C. Reinhardt. 2009. Bispecific T-cell engaging antibodies for cancer therapy. Cancer Res. 69: 4941-4944.
3. Pillay, V., H. K. Gan, and A. M. Scott. 2011. Antibodies in oncology. New Biotechnol. 28: 518-529.
4. Jachimowicz, R. D., S. Borchmann, and A. Rothe. 2014. Multi-specific antibodies for cancer immunotherapy. BioDrugs 28: 331-343.
5. Burnet, F. M. 1971. Immunological surveillance in neoplasia. Transplant. Rev. 7: 3-25.
6. Schreiber, R. D., L. J. Old, and M. J. Smyth. 2011. Cancer immunoediting: integrating immunity's roles in cancer suppression and promotion. Science 331: 1565-1570.
7. Bottino, C., L. Moretta, and A. Moretta. 2006. NK cell activating receptors and tumor recognition in humans. Curr. Top. Microbiol. Immunol. 298: 175-182.
8. Faveeuw, C., and F. Trottein. 2014. Optimization of natural killer T cell-mediated immunotherapy in cancer using cell-based and nanovector vaccines. Cancer Res. 74: 1632-1638.
9. Jiang, J., C. Wu, and B. Lu. 2013. Cytokine-induced killer cells promote antitumor immunity. J. Transl. Med. 11: 83.
10. Koretz, K., G. Moldenhauer, O. Majdic, and P. Möller. 1989. Correlation of HLA-D/Ii antigen expression in breast carcinoma with local lymphohistiocytic infiltration reveals considerable dysregulation in a subset of tumors. Int. J. Cancer 44: 816-822.
11. Marincola, F. M., E. M. Jaffee, D. J. Hicklin, and S. Ferrone. 2000. Escape of human solid tumors from T-cell recognition: molecular mechanisms and functional significance. Adv. Immunol. 74: 181-273.
12. Möller, P., T. Mattfeldt, C. Gross, P. Schlosshauer, A. Koch, K. Koretz, G. Moldenhauer, M. Kaufmann, and H. F. Otto. 1989. Expression of HLA-A, -B, -C, -DR, -DP, -DQ, and of HLA-D-associated invariant chain (Ii) in non-neoplastic mammary epithelium, fibroadenoma, adenoma, and carcinoma of the breast. Am. J. Pathol. 135: 73-83.
13. Offringa, R., S. H. van der Burg, F. Ossendorp, R. E. Toes, and C. J. Melief. 2000. Design and evaluation of antigen-specific vaccination strategies against cancer. Curr. Opin. Immunol. 12: 576-582.
14. Brossart, P., G. Stuhler, T. Flad, S. Stevanovic, H. G. Rammensee, L. Kanz, and W. Brugger. 1998. Her-2/neu-derived peptides are tumor-associated antigens expressed by human renal cell and colon carcinoma lines and are recognized by in vitro induced specific cytotoxic T lymphocytes. Cancer Res. 58: 732-736.
15. Molldrem, J. J., P. P. Lee, C. Wang, K. Felio, H. M. Kantarjian, R. E. Champlin, and M. M. Davis. 2000. Evidence that specific T lymphocytes may participate in the elimination of chronic myelogenous leukemia. Nat. Med. 6: 1018-1023.
16. Filaci, G., M. Fravega, M. Setti, P. Traverso, E. Millo, D. Fenoglio, S. Negrini, F. Ferrera, A. Romagnoli, M. Basso, et al. 2006. Frequency of telomerase-specific CD8+ T lymphocytes in patients with cancer. Blood 107: 1505-1512.
17. Ahmadzadeh, M., L. A. Johnson, B. Heemskerk, J. R. Wunderlich, M. E. Dudley, D. E. White, and S. A. Rosenberg. 2009. Tumor antigen-specific CD8 T cells infiltrating the tumor express high levels of PD-1 and are functionally impaired. Blood 114: 1537-1544.
18. Rosenberg, S. A., J. C. Yang, D. J. Schwartzentruber, P. Hwu, F. M. Marincola, S. L. Topalian, N. P. Restifo, M. E. Dudley, S. L. Schwarz, P. J. Spiess, et al. 1998. Immunologic and therapeutic evaluation of a synthetic peptide vaccine for the treatment of patients with metastatic melanoma. Nat. Med. 4: 321-327.
19. Rosenberg, S. A., J. C. Yang, and N. P. Restifo. 2004. Cancer immunotherapy: moving beyond current vaccines. Nat. Med. 10: 909-915.
20. Klebanoff, C. A., N. Acquavella, Z. Yu, and N. P. Restifo. 2011. Therapeutic cancer vaccines: are we there yet? Immunol. Rev. 239: 27-44.
21. Flemming, A. 2014. Deal watch: Pfizer and GSK join race for T cell cancer therapies. Nat. Rev. Drug Discov. 13: 568-569.
22. June, C., S. A. Rosenberg, M. Sadelain, and J. S. Weber. 2012. T-cell therapy at the threshold. Nat. Biotechnol. 30: 611-614.
23. Porter, D. L., B. L. Levine, M. Kalos, A. Bagg, and C. H. June. 2011. Chimeric antigen receptor-modified T cells in chronic lymphoid leukemia. N. Engl. J. Med. 365: 725-733.
24. Kochenderfer, J. N., M. E. Dudley, S. A. Feldman, W. H. Wilson, D. E. Spaner, I. Maric, M. Stetler-Stevenson, G. Q. Phan, M. S. Hughes, R. M. Sherry, et al. 2012. B-cell depletion and remissions of malignancy along with cytokine-associated toxicity in a clinical trial of anti-CD19 chimeric-antigen-receptor-transduced T cells. Blood 119: 2709-2720.
25. Vacchelli, E., A. Eggermont, W. H. Fridman, J. Galon, E. Tartour, L. Zitvogel, G. Kroemer, and L. Galluzzi. 2013. Trial Watch: Adoptive cell transfer for anticancer immunotherapy. OncoImmunology 2: e24238.
26. Ruella, M., and M. Kalos. 2014. Adoptive immunotherapy for cancer. Immunol. Rev. 257: 14-38.
27. Couzin-Frankel, J. 2013. Breakthrough of the year 2013. Cancer immunotherapy. Science 342: 1432-1433.
28. Kim, H. J., and H. Cantor. 2014. CD4 T-cell subsets and tumor immunity: the helpful and the not-so-helpful. Cancer Immunol Res 2: 91-98.
29. Claman, H. N., E. A. Chaperon, and R. F. Triplett. 1966. Thymus-marrow cell combinations. Synergism in antibody production. Proc. Soc. Exp. Biol. Med. 122: 1167-1171.
30. Mitchison, N. A. 1971. The carrier effect in the secondary response to haptenprotein conjugates. II. Cellular cooperation. Eur. J. Immunol. 1: 18-27.
31. Lanzavecchia, A. 1985. Antigen-specific interaction between T and B cells. Nature 314: 537-539.
32. Bretscher, P., and M. Cohn. 1970. A theory of self-nonself discrimination. Science 169: 1042-1049.
33. Lake, P., and N. A. Mitchison. 1977. Regulatory mechanisms in the immune response to cell-surface antigens. Cold Spring Harb. Symp. Quant. Biol. 41: 589-595.
34. Cohn, M. 2005. The common sense of the self-nonself discrimination. Springer Semin. Immunopathol. 27: 3-17.
35. Cassell, D., and J. Forman. 1988. Linked recognition of helper and cytotoxic antigenic determinants for the generation of cytotoxic T lymphocytes. Ann. N. Y. Acad. Sci. 532: 51-60.
36. Janssen, E. M., E. E. Lemmens, T. Wolfe, U. Christen, M. G. von Herrath, and S. P. Schoenberger. 2003. CD4+ T cells are required for secondary expansion and memory in CD8+ T lymphocytes. Nature 421: 852-856.
37. Shedlock, D. J., and H. Shen. 2003. Requirement for CD4 T cell help in generating functional CD8 T cell memory. Science 300: 337-339.
38. Sun, J. C., and M. J. Bevan. 2003. Defective CD8 T cell memory following acute infection without CD4 T cell help. Science 300: 339-342.
39. Langlade-Demoyen, P., F. Garcia-Pons, P. Castiglioni, Z. Garcia, S. Cardinaud, S. Xiong, M. Gerloni, and M. Zanetti. 2003. Role of T cell help and endoplasmic reticulum targeting in protective CTL response against influenza virus. Eur. J. Immunol. 33: 720-728.
40. Mosmann, T. R., and R. L. Coffman. 1989. TH1 and TH2 cells: different patterns of lymphokine secretion lead to different functional properties. Annu. Rev. Immunol. 7: 145-173.
41. Sakaguchi, S., N. Sakaguchi, J. Shimizu, S. Yamazaki, T. Sakihama, M. Itoh, Y. Kuniyasu, T. Nomura, M. Toda, and T. Takahashi. 2001. Immunologic tolerance maintained by CD25+ CD4+ regulatory T cells: their common role in controlling autoimmunity, tumor immunity, and transplantation tolerance. Immunol. Rev. 182: 18-32.
42. Crotty, S. 2011. Follicular helper CD4 T cells (TFH). Annu. Rev. Immunol. 29: 621-663.
43. Greenberg, P. D., M. A. Cheever, and A. Fefer. 1981. Eradication of disseminated murine leukemia by chemoimmunotherapy with cyclophosphamide and adoptively transferred immune syngeneic Lyt-1+2- lymphocytes. J. Exp. Med. 154: 952-963.
44. Fujiwara, H., M. Fukuzawa, T. Yoshioka, H. Nakajima, and T. Hamaoka. 1984. The role of tumor-specific Lyt-1+22 - T cells in eradicating tumor cells in vivo. I. Lyt-1+22 - T cells do not necessarily require recruitment of host's cytotoxic T cell precursors for implementation of in vivo immunity. J. Immunol. 133: 1671-1676.
45. Hock, H., M. Dorsch, T. Diamantstein, and T. Blankenstein. 1991. Interleukin 7 induces CD4+ T cell-dependent tumor rejection. J. Exp. Med. 174: 1291-1298.
46. Lauritzsen, G. F., S. Weiss, Z. Dembic, and B. Bogen. 1994. Naive idiotype-specific CD4+ T cells and immunosurveillance of B-cell tumors. Proc. Natl. Acad. Sci. USA 91: 5700-5704.
47. Hung, K., R. Hayashi, A. Lafond-Walker, C. Lowenstein, D. Pardoll, and H. Levitsky. 1998. The central role of CD4(+) T cells in the antitumor immune response. J. Exp. Med. 188: 2357-2368.
48. Mumberg, D., P. A. Monach, S. Wanderling, M. Philip, A. Y. Toledano, R. D. Schreiber, and H. Schreiber. 1999. CD4(+) T cells eliminate MHC class IInegative cancer cells in vivo by indirect effects of IFN-gamma. Proc. Natl. Acad. Sci. USA 96: 8633-8638.
49. Tempero, R. M., M. L. VanLith, K. Morikane, G. J. Rowse, S. J. Gendler, and M. A. Hollingsworth. 1998. CD4+ lymphocytes provide MUC1-specific tumor immunity in vivo that is undetectable in vitro and is absent in MUC1 transgenic mice. J. Immunol. 161: 5500-5506.
50. Greenberg, P. D. 1991. Adoptive T cell therapy of tumors: mechanisms operative in the recognition and elimination of tumor cells. Adv. Immunol. 49: 281-355.
51. Dighe, A. S., E. Richards, L. J. Old, and R. D. Schreiber. 1994. Enhanced in vivo growth and resistance to rejection of tumor cells expressing dominant negative IFN gamma receptors. Immunity 1: 447-456.
52. Williamson, B. D., E. A. Carswell, B. Y. Rubin, J. S. Prendergast, and L. J. Old. 1983. Human tumor necrosis factor produced by human B-cell lines: synergistic cytotoxic interaction with human interferon. Proc. Natl. Acad. Sci. USA 80: 5397-5401.
53. Fransen, L., J. Van der Heyden, R. Ruysschaert, and W. Fiers. 1986. Recombinant tumor necrosis factor: its effect and its synergism with interferon-gamma on a variety of normal and transformed human cell lines. Eur. J. Cancer Clin. Oncol. 22: 419-426.
54. Coughlin, C. M., K. E. Salhany, M. S. Gee, D. C. LaTemple, S. Kotenko, X. Ma, G. Gri, M. Wysocka, J. E. Kim, L. Liu, et al. 1998. Tumor cell responses to IFNgamma affect tumorigenicity and response to IL-12 therapy and antiangiogenesis. Immunity 9: 25-34.
55. Qin, Z., and T. Blankenstein. 2000. CD4+ T cell-mediated tumor rejection involves inhibition of angiogenesis that is dependent on IFN gamma receptor expression by nonhematopoietic cells. Immunity 12: 677-686.
56. Corthay, A., D. K. Skovseth, K. U. Lundin, E. Røsjø, H. Omholt, P. O. Hofgaard, G. Haraldsen, and B. Bogen. 2005. Primary antitumor immune response mediated by CD4+ T cells. Immunity 22: 371-383.
57. Haabeth, O. A., K. B. Lorvik, C. Hammarström, I. M. Donaldson, G. Haraldsen, B. Bogen, and A. Corthay. 2011. Inflammation driven by tumour-specific Th1 cells protects against B-cell cancer. Nat. Commun. 2: 240.
58. Xie, Y., A. Akpinarli, C. Maris, E. L. Hipkiss, M. Lane, E. K. Kwon, P. Muranski, N. P. Restifo, and P. A. Antony. 2010. Naive tumor-specific CD4(+) T cells differentiated in vivo eradicate established melanoma. J. Exp. Med. 207: 651-667.
59. Quezada, S. A., T. R. Simpson, K. S. Peggs, T. Merghoub, J. Vider, X. Fan, R. Blasberg, H. Yagita, P. Muranski, P. A. Antony, et al. 2010. Tumor-reactive CD4(+) T cells develop cytotoxic activity and eradicate large established melanoma after transfer into lymphopenic hosts. J. Exp. Med. 207: 637-650.
60. Horna, P., A. Cuenca, F. Cheng, J. Brayer, H. W. Wang, I. Borrello, H. Levitsky, and E. M. Sotomayor. 2006. In vivo disruption of tolerogenic cross-presentation mechanisms uncovers an effective T-cell activation by B-cell lymphomas leading to antitumor immunity. Blood 107: 2871-2878.
61. Perez-Diez, A., N. T. Joncker, K. Choi, W. F. Chan, C. C. Anderson, O. Lantz, and P. Matzinger. 2007. CD4 cells can be more efficient at tumor rejection than CD8 cells. Blood 109: 5346-5354.
62. Vlad, A. M., S. Muller, M. Cudic, H. Paulsen, L. Otvos, Jr., F. G. Hanisch, and O. J. Finn. 2002. Complex carbohydrates are not removed during processing of glycoproteins by dendritic cells: processing of tumor antigen MUC1 glycopeptides for presentation to major histocompatibility complex class II-restricted T cells. J. Exp. Med. 196: 1435-1446.
63. Mucida, D., M. M. Husain, S. Muroi, F. van Wijk, R. Shinnakasu, Y. Naoe, B. S. Reis, Y. Huang, F. Lambolez, M. Docherty, et al. 2013. Transcriptional reprogramming of mature CD4+ helper T cells generates distinct MHC class II-restricted cytotoxic T lymphocytes. Nat. Immunol. 14: 281-289.
64. Zeng, G., C. E. Touloukian, X. Wang, N. P. Restifo, S. A. Rosenberg, and R. F. Wang. 2000. Identification of CD4+ T cell epitopes from NY-ESO-1 presented by HLA-DR molecules. J. Immunol. 165: 1153-1159.
65. Zeng, G., X. Wang, P. F. Robbins, S. A. Rosenberg, and R. F. Wang. 2001. CD4 (+) T cell recognition of MHC class II-restricted epitopes from NY-ESO-1 presented by a prevalent HLA DP4 allele: association with NY-ESO-1 antibody production. Proc. Natl. Acad. Sci. USA 98: 3964-3969.
66. Campi, G., M. Crosti, G. Consogno, V. Facchinetti, B. M. Conti-Fine, R. Longhi, G. Casorati, P. Dellabona, and M. P. Protti. 2003. CD4(+) T cells from healthy subjects and colon cancer patients recognize a carcinoembryonic antigen-specific immunodominant epitope. Cancer Res. 63: 8481-8486.
67. Kudela, P., Z. Sun, J. Fourcade, B. Janjic, J. M. Kirkwood, B. Maillere, and H. M. Zarour. 2011. Epitope hierarchy of spontaneous CD4+ T cell responses to LAGE-1. J. Immunol. 186: 312-322.
68. Ohue, Y., S. Eikawa, N. Okazaki, Y. Mizote, M. Isobe, A. Uenaka, M. Fukuda, L. J. Old, M. Oka, and E. Nakayama. 2012. Spontaneous antibody, and CD4 and CD8 T-cell responses against XAGE-1b (GAGED2a) in non-small cell lung cancer patients. Int. J. Cancer 131: E649-E658.
69. Tsuji, T., J. Matsuzaki, E. Ritter, A. Miliotto, G. Ritter, K. Odunsi, L. J. Old, and S. Gnjatic. 2011. Split T cell tolerance against a self/tumor antigen: spontaneous CD4+ but not CD8+ T cell responses against p53 in cancer patients and healthy donors. PLoS ONE 6: e23651.
70. Munir, S., S. K. Larsen, T. Z. Iversen, M. Donia, T. W. Klausen, I. M. Svane, P. T. Straten, and M. H. Andersen. 2012. Natural CD4+ T-cell responses against indoleamine 2,3-dioxygenase. PLoS ONE 7: e34568.
71. Galon, J., A. Costes, F. Sanchez-Cabo, A. Kirilovsky, B. Mlecnik, C. Lagorce-Pagès, M. Tosolini, M. Camus, A. Berger, P. Wind, et al. 2006. Type, density, and location of immune cells within human colorectal tumors predict clinical outcome. Science 313: 1960-1964.
72. Yoshida, N., H. Abe, T. Ohkuri, D. Wakita, M. Sato, D. Noguchi, M. Miyamoto, T. Morikawa, S. Kondo, H. Ikeda, and T. Nishimura. 2006. Expression of the MAGE-A4 and NY-ESO-1 cancer-testis antigens and T cell infiltration in non-small cell lung carcinoma and their prognostic significance. Int. J. Oncol. 28: 1089-1098.
73. Ayyoub, M., P. Pignon, J. M. Classe, K. Odunsi, and D. Valmori. 2013. CD4+ T effectors specific for the tumor antigen NY-ESO-1 are highly enriched at ovarian cancer sites and coexist with, but are distinct from, tumor-associated Treg. Cancer Immunol Res 1: 303-308.
74. Moreno, A., P. Clavijo, R. Edelman, J. Davis, M. Sztein, D. Herrington, and E. Nardin. 1991. Cytotoxic CD4+ T cells from a sporozoite-immunized volunteer recognize the Plasmodium falciparum CS protein. Int. Immunol. 3: 997-1003.
75. Barnaba, V., A. Franco, M. Paroli, R. Benvenuto, G. De Petrillo, V. L. Burgio, I. Santilio, C. Balsano, M. S. Bonavita, G. Cappelli, et al. 1994. Selective expansion of cytotoxic T lymphocytes with a CD4+CD56+ surface phenotype and a T helper type 1 profile of cytokine secretion in the liver of patients chronically infected with Hepatitis B virus. J. Immunol. 152: 3074-3087.
76. Nisini, R., M. Paroli, D. Accapezzato, F. Bonino, F. Rosina, T. Santantonio, F. Sallusto, A. Amoroso, M. Houghton, and V. Barnaba. 1997. Human CD4+ T-cell response to hepatitis delta virus: identification of multiple epitopes and characterization of T-helper cytokine profiles. J. Virol. 71: 2241-2251.
77. Thomas, W. D., and P. Hersey. 1998. CD4 T cells kill melanoma cells by mechanisms that are independent of Fas (CD95). Int. J. Cancer 75: 384-390.
78. Soghoian, D. Z., H. Jessen, M. Flanders, K. Sierra-Davidson, S. Cutler, T. Pertel, S. Ranasinghe, M. Lindqvist, I. Davis, K. Lane, et al. 2012. HIV-specific cytolytic CD4 T cell responses during acute HIV infection predict disease outcome. Sci. Transl. Med. 4: 23ra25.
79. Manici, S., T. Sturniolo, M. A. Imro, J. Hammer, F. Sinigaglia, C. Noppen, G. Spagnoli, B. Mazzi, M. Bellone, P. Dellabona, and M. P. Protti. 1999. Melanoma cells present a MAGE-3 epitope to CD4(+) cytotoxic T cells in association with histocompatibility leukocyte antigen DR11. J. Exp. Med. 189: 871-876.
80. Hombach, A., H. Köhler, G. Rappl, and H. Abken. 2006. Human CD4+ T cells lyse target cells via granzyme/perforin upon circumvention of MHC class II restriction by an antibody-like immunoreceptor. J. Immunol. 177: 5668-5675.
81. Hess, S. D., N. K. Egilmez, N. Bailey, T. M. Anderson, E. Mathiowitz, S. H. Bernstein, and R. B. Bankert. 2003. Human CD4+ T cells present within the microenvironment of human lung tumors are mobilized by the local and sustained release of IL-12 to kill tumors in situ by indirect effects of IFN-gamma. J. Immunol. 170: 400-412.
82. Viola, A., and A. Lanzavecchia. 1996. T cell activation determined by T cell receptor number and tunable thresholds. Science 273: 104-106.
83. Sykulev, Y., M. Joo, I. Vturina, T. J. Tsomides, and H. N. Eisen. 1996. Evidence that a single peptide-MHC complex on a target cell can elicit a cytolytic T cell response. Immunity 4: 565-571.
84. Sercarz, E. E., P. V. Lehmann, A. Ametani, G. Benichou, A. Miller, and K. Moudgil. 1993. Dominance and crypticity of T cell antigenic determinants. Annu. Rev. Immunol. 11: 729-766.
85. Gabrilovich, D. I., S. Ostrand-Rosenberg, and V. Bronte. 2012. Coordinated regulation of myeloid cells by tumours. Nat. Rev. Immunol. 12: 253-268.
86. Kappler, J. W., N. Roehm, and P. Marrack. 1987. T cell tolerance by clonal elimination in the thymus. Cell 49: 273-280.
87. Cobbold, S. P., E. Adams, S. E. Marshall, J. D. Davies, and H. Waldmann. 1996. Mechanisms of peripheral tolerance and suppression induced by monoclonal antibodies to CD4 and CD8. Immunol. Rev. 149: 5-33.
88. Ochsenbein, A. F., P. Klenerman, U. Karrer, B. Ludewig, M. Pericin, H. Hengartner, and R. M. Zinkernagel. 1999. Immune surveillance against a solid tumor fails because of immunological ignorance. Proc. Natl. Acad. Sci. USA 96: 2233-2238.
89. Mahadevan, N. R., and M. Zanetti. 2011. Tumor stress inside out: cell-extrinsic effects of the unfolded protein response in tumor cells modulate the immunological landscape of the tumor microenvironment. J. Immunol. 187: 4403-4409.
90. Wing, K., and S. Sakaguchi. 2010. Regulatory T cells exert checks and balances on self tolerance and autoimmunity. Nat. Immunol. 11: 7-13.
91. Grivennikov, S. I., F. R. Greten, and M. Karin. 2010. Immunity, inflammation, and cancer. Cell 140: 883-899.
92. Willimsky, G., and T. Blankenstein. 2005. Sporadic immunogenic tumours avoid destruction by inducing T-cell tolerance. Nature 437: 141-146.
93. Monsurrò, V., E. Wang, Y. Yamano, S. A. Migueles, M. C. Panelli, K. Smith, D. Nagorsen, M. Connors, S. Jacobson, and F. M. Marincola. 2004. Quiescent phenotype of tumor-specific CD8+ T cells following immunization. Blood 104: 1970-1978.
94. Schietinger, A., J. J. Delrow, R. S. Basom, J. N. Blattman, and P. D. Greenberg. 2012. Rescued tolerant CD8 T cells are preprogrammed to reestablish the tolerant state. Science 335: 723-727.
95. Brahmer, J. R., S. S. Tykodi, L. Q. Chow, W. J. Hwu, S. L. Topalian, P. Hwu, C. G. Drake, L. H. Camacho, J. Kauh, K. Odunsi, et al. 2012. Safety and activity of anti-PD-L1 antibody in patients with advanced cancer. N. Engl. J. Med. 366: 2455-2465.
96. Topalian, S. L., F. S. Hodi, J. R. Brahmer, S. N. Gettinger, D. C. Smith, D. F. McDermott, J. D. Powderly, R. D. Carvajal, J. A. Sosman, M. B. Atkins, et al. 2012. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N. Engl. J. Med. 366: 2443-2454.
97. Gerloni, M., S. Xiong, S. Mukerjee, S. P. Schoenberger, M. Croft, and M. Zanetti. 2000. Functional cooperation between T helper cell determinants. Proc. Natl. Acad. Sci. USA 97: 13269-13274.
98. Gerloni, M., and M. Zanetti. 2005. CD4 T cells in tumor immunity. Springer Semin. Immunopathol. 27: 37-48.
99. Gerloni, M., P. Castiglioni, and M. Zanetti. 2005. The cooperation between two CD4 T cells induces tumor protective immunity in MUC.1 transgenic mice. J. Immunol. 175: 6551-6559.
100. Bretscher, P. A. 1986. A cascade of T-T interactions, mediated by the linked recognition of antigen, in the induction of T cells able to help delayed-type hypersensitivity responses. J. Immunol. 137: 3726-3733.
101. Bretscher, P. A. 1999. A two-step, two-signal model for the primary activation of precursor helper T cells. Proc. Natl. Acad. Sci. USA 96: 185-190.
102. Zanetti, M. 2005. T for two: when helpers need help. Autoimmun. Rev. 4: 571-578.
103. Schoenberger, S. P., R. E. Toes, E. I. van der Voort, R. Offringa, and C. J. Melief. 1998. T-cell help for cytotoxic T lymphocytes is mediated by CD40-CD40L interactions. Nature 393: 480-483.
104. den Haan, J. M., and M. J. Bevan. 2000. A novel helper role for CD4 T cells. Proc. Natl. Acad. Sci. USA 97: 12950-12952.
105. Kyte, J. A. 2009. Cancer vaccination with telomerase peptide GV1001. Expert Opin. Investig. Drugs 18: 687-694.
106. Silverstein, A. M. 1989. A History of Immunology. Academic Press, San Diego, CA.
107. Savelyeva, N., R.Munday,M. B. Spellerberg, G. P. Lomonossoff, and F. K. Stevenson. 2001. Plant viral genes in DNA idiotypic vaccines activate linked CD4+ T-cell mediated immunity against B-cell malignancies. Nat. Biotechnol. 19: 760-764.
108. Stevenson, F. K., C. H. Ottensmeier, P. Johnson, D. Zhu, S. L. Buchan, K. J. McCann, J. S. Roddick, A. T. King, F. McNicholl, N. Savelyeva, and J. Rice. 2004. DNA vaccines to attack cancer. Proc. Natl. Acad. Sci. USA 101(Suppl. 2): 14646-14652.
109. Facciabene, A., L. Aurisicchio, L. Elia, F. Palombo, C. Mennuni, G. Ciliberto, and N. La Monica. 2006. DNA and adenoviral vectors encoding carcinoembryonic antigen fused to immunoenhancing sequences augment antigen-specific immune response and confer tumor protection. Hum. Gene Ther. 17: 81-92.
110. Snook, A. E., M. S. Magee, S. Schulz, and S. A. Waldman. 2014. Selective antigen-specific CD4(+) T-cell, but not CD8(+) T- or B-cell, tolerance corrupts cancer immunotherapy. Eur. J. Immunol. 44: 1956-1966.
111. Kobayashi, H., M. Wood, Y. Song, E. Appella, and E. Celis. 2000. Defining promiscuous MHC class II helper T-cell epitopes for the HER2/neu tumor antigen. Cancer Res. 60: 5228-5236.
112. Zarour, H. M., B. Maillere, V. Brusic, K. Coval, E. Williams, S. Pouvelle-Moratille, F. Castelli, S. Land, J. Bennouna, T. Logan, and J. M. Kirkwood. 2002. NY-ESO-1 119-143 is a promiscuous major histocompatibility complex class II T-helper epitope recognized by Th1- and Th2-type tumor-reactive CD4+ T cells. Cancer Res. 62: 213-218.
113. Consogno, G., S. Manici, V. Facchinetti, A. Bachi, J. Hammer, B. M. Conti-Fine, C. Rugarli, C. Traversari, and M. P. Protti. 2003. Identification of immunodominant regions among promiscuous HLA-DR-restricted CD4+ T-cell epitopes on the tumor antigen MAGE-3. Blood 101: 1038-1044.
114. Neumann, F., C. Wagner, S. Stevanovic, B. Kubuschok, C. Schormann, A. Mischo, K. Ertan, W. Schmidt, and M. Pfreundschuh. 2004. Identification of an HLA-DRrestricted peptide epitope with a promiscuous binding pattern derived from the cancer testis antigen HOM-MEL-40/SSX2. Int. J. Cancer 112: 661-668.
115. Wang, X. F., J. Kerzerho, O. Adotevi, H. Nuyttens, C. Badoual, G. Munier, S. Oudard, S. Tu, E. Tartour, and B. Maillère. 2008. Comprehensive analysis of HLA-DR-and HLA-DP4-restricted CD4+ T cell response specific for the tumor-shared antigen survivin in healthy donors and cancer patients. J. Immunol. 181: 431-439.
116. Pieper, R., R. E. Christian, M. I. Gonzales, M. I. Nishimura, G. Gupta, R. E. Settlage, J. Shabanowitz, S. A. Rosenberg, D. F. Hunt, and S. L. Topalian. 1999. Biochemical identification of a mutated human melanoma antigen recognized by CD4(+) T cells. J. Exp. Med. 189: 757-766.
117. Wang, R. F., X. Wang, and S. A. Rosenberg. 1999. Identification of a novel major histocompatibility complex class II-restricted tumor antigen resulting from a chromosomal rearrangement recognized by CD4(+) T cells. J. Exp. Med. 189: 1659-1668.
118. Wang, R. F., X. Wang, A. C. Atwood, S. L. Topalian, and S. A. Rosenberg. 1999. Cloning genes encoding MHC class II-restricted antigens: mutated CDC27 as a tumor antigen. Science 284: 1351-1354.
119. Joseph, C. G., E. Darrah, A. A. Shah, A. D. Skora, L. A. Casciola-Rosen, F. M. Wigley, F. Boin, A. Fava, C. Thoburn, I. Kinde, et al. 2014. Association of the autoimmune disease scleroderma with an immunologic response to cancer. Science 343: 152-157.
120. Vigneron, N., V. Stroobant, B. J. Van den Eynde, and P. van der Bruggen. 2013. Database of T cell-defined human tumor antigens: the 2013 update. Cancer Immun. 13: 15.
121. Tran, E., S. Turcotte, A. Gros, P. F. Robbins, Y. C. Lu, M. E. Dudley, J. R. Wunderlich, R. P. Somerville, K. Hogan, C. S. Hinrichs, et al. 2014. Cancer immunotherapy based on mutation-specific CD4+ T cells in a patient with epithelial cancer. Science 344: 641-645.
122. Yotnda, P., H. Firat, F. Garcia-Pons, Z. Garcia, G. Gourru, J. P. Vernant, F. A. Lemonnier, V. Leblond, and P. Langlade-Demoyen. 1998. Cytotoxic T cell response against the chimeric p210 BCR-ABL protein in patients with chronic myelogenous leukemia. J. Clin. Invest. 101: 2290-2296.
123. Kissick, H. T., M. G. Sanda, L. K. Dunn, K. L. Pellegrini, S. T. On, J. K. Noel, and M. S. Arredouani. 2014. Androgens alter T-cell immunity by inhibiting T-helper 1 differentiation. Proc. Natl. Acad. Sci. USA 111: 9887-9892.
124. van der Bruggen, P., V. Stroobant, N. Vigneron, and B. Van den Eynde. 2013. Peptide Database: T Cell-Defined Tumor Antigens. Available at: http://www.cancerimmunity.org/peptide/. Accessed: November 2014.
125. Vogelstein, B., N. Papadopoulos, V. E. Velculescu, S. Zhou, L. A. Diaz, Jr., and K. W. Kinzler. 2013. Cancer genome landscapes. Science 339: 1546-1558.
126. Marusyk, A., V. Almendro, and K. Polyak. 2012. Intra-tumour heterogeneity: a looking glass for cancer? Nat. Rev. Cancer 12: 323-334.
127. Schumacher, T., L. Bunse, S. Pusch, F. Sahm, B. Wiestler, J. Quandt, O. Menn, M. Osswald, I. Oezen, M. Ott, et al. 2014. A vaccine targeting mutant IDH1 induces antitumour immunity. Nature 512: 324-327.
128. Ding, L., M. J. Ellis, S. Li, D. E. Larson, K. Chen, J. W. Wallis, C. C. Harris, M. D. McLellan, R. S. Fulton, L. L. Fulton, et al. 2010. Genome remodelling in a basal-like breast cancer metastasis and xenograft. Nature 464: 999-1005.
129. Gerlinger, M., A. J. Rowan, S. Horswell, J. Larkin, D. Endesfelder, E. Gronroos, P. Martinez, N. Matthews, A. Stewart, P. Tarpey, et al. 2012. Intratumor heterogeneity and branched evolution revealed by multiregion sequencing. N. Engl. J. Med. 366: 883-892.
130. Burrell, R. A., N. McGranahan, J. Bartek, and C. Swanton. 2013. The causes and consequences of genetic heterogeneity in cancer evolution. Nature 501: 338-345.
131. Nik-Zainal, S., L. B. Alexandrov, D. C. Wedge, P. Van Loo, C. D. Greenman, K. Raine, D. Jones, J. Hinton, J. Marshall, L. A. Stebbings, et al Breast Cancer Working Group of the International Cancer Genome Consortium. 2012. Mutational processes molding the genomes of 21 breast cancers. Cell 149: 979-993.
132. Zhang, J., J. Fujimoto, J. Zhang, D. C. Wedge, X. Song, J. Zhang, S. Seth, C. W. Chow, Y. Cao, C. Gumbs, et al. 2014. Intratumor heterogeneity in localized lung adenocarcinomas delineated by multiregion sequencing. Science 346: 256-259.
133. Sampson, J. H., A. B. Heimberger, G. E. Archer, K. D. Aldape, A. H. Friedman, H. S. Friedman, M. R. Gilbert, J. E. Herndon, II, R. E. McLendon, D. A. Mitchell, et al. 2010. Immunologic escape after prolonged progression-free survival with epidermal growth factor receptor variant III peptide vaccination in patients with newly diagnosed glioblastoma. J. Clin. Oncol. 28: 4722-4729.
134. Lehmann, P. V., T. Forsthuber, A. Miller, and E. E. Sercarz. 1992. Spreading of T-cell autoimmunity to cryptic determinants of an autoantigen. Nature 358: 155-157.
135. Vanderlugt, C. L., and S. D. Miller. 2002. Epitope spreading in immune-mediated diseases: implications for immunotherapy. Nat. Rev. Immunol. 2: 85-95.
136. Kreso, A., C. A. O'Brien, P. van Galen, O. I. Gan, F. Notta, A. M. Brown, K. Ng, J. Ma, E. Wienholds, C. Dunant, et al. 2013. Variable clonal repopulation dynamics influence chemotherapy response in colorectal cancer. Science 339: 543-548.
137. Marusyk, A., D. P. Tabassum, P. M. Altrock, V. Almendro, F. Michor, and K. Polyak. 2014. Non-cell-autonomous driving of tumour growth supports subclonal heterogeneity. Nature 514: 54-58.
138. van Galen, P., A. Kreso, N. Mbong, D. G. Kent, T. Fitzmaurice, J. E. Chambers, S. Xie, E. Laurenti, K. Hermans, K. Eppert, et al. 2014. The unfolded protein response governs integrity of the haematopoietic stem-cell pool during stress. Nature 510: 268-272.
139. Schroers, R., L. Shen, L. Rollins, C. M. Rooney, K. Slawin, G. Sonderstrup, X. F. Huang, and S. Y. Chen. 2003. Human telomerase reverse transcriptase-specific T-helper responses induced by promiscuous major histocompatibility complex class II-restricted epitopes. Clin. Cancer Res. 9: 4743-4755.
140. Brunsvig, P. F., J. A. Kyte, C. Kersten, S. Sundstrøm, M. Møller, M. Nyakas, G. L. Hansen, G. Gaudernack, and S. Aamdal. 2011. Telomerase peptide vaccination in NSCLC: a phase II trial in stage III patients vaccinated after chemoradiotherapy and an 8-year update on a phase I/II trial. Clin. Cancer Res. 17: 6847-6857.
141. Dosset, M., Y. Godet, C. Vauchy, L. Beziaud, Y. C. Lone, C. Sedlik, C. Liard, E. Levionnois, B. Clerc, F. Sandoval, et al. 2012. Universal cancer peptide-based therapeutic vaccine breaks tolerance against telomerase and eradicates established tumor. Clin. Cancer Res. 18: 6284-6295.
142. Widenmeyer, M., H. Griesemann, S. Stevanović, S. Feyerabend, R. Klein, S. Attig, J. Hennenlotter, D. Wernet, D. V. Kuprash, A. Y. Sazykin, et al. 2012. Promiscuous survivin peptide induces robust CD4+ T-cell responses in the majority of vaccinated cancer patients. Int. J. Cancer 131: 140-149.
143. Kimura, T., J. R. McKolanis, L. A. Dzubinski, K. Islam, D. M. Potter, A. M. Salazar, R. E. Schoen, and O. J. Finn. 2013. MUC1 vaccine for individuals with advanced adenoma of the colon: a cancer immunoprevention feasibility study. Cancer Prev. Res. (Phila.) 6: 18-26.
144. Wierecky, J., M. R. Müller, S. Wirths, E. Halder-Oehler, D. Dörfel, S. M. Schmidt, M. Häntschel, W. Brugger, S. Schröder, M. S. Horger, et al. 2006. Immunologic and clinical responses after vaccinations with peptide-pulsed dendritic cells in metastatic renal cancer patients. Cancer Res. 66: 5910-5918.
145. Nishikawa, H., E. Sato, G. Briones, L. M. Chen, M. Matsuo, Y. Nagata, G. Ritter, E. Jäger, H. Nomura, S. Kondo, et al. 2006. In vivo antigen delivery by a Salmonella typhimurium type III secretion system for therapeutic cancer vaccines. J. Clin. Invest. 116: 1946-1954.
146. Hunder, N. N., H. Wallen, J. Cao, D. W. Hendricks, J. Z. Reilly, R. Rodmyre, A. Jungbluth, S. Gnjatic, J. A. Thompson, and C. Yee. 2008. Treatment of metastatic melanoma with autologous CD4+ T cells against NY-ESO-1. N. Engl. J. Med. 358: 2698-2703.
147. Carmichael, M. G., L. C. Benavides, J. P. Holmes, J. D. Gates, E. A. Mittendorf, S. Ponniah, and G. E. Peoples. 2010. Results of the first phase 1 clinical trial of the HER-2/neu peptide (GP2) vaccine in disease-free breast cancer patients: United States Military Cancer Institute Clinical Trials Group Study I-04. Cancer 116: 292-301.
148. Friedman, K. M., P. A. Prieto, L. E. Devillier, C. A. Gross, J. C. Yang, J. R. Wunderlich, S. A. Rosenberg, and M. E. Dudley. 2012. Tumor-specific CD4+ melanoma tumor-infiltrating lymphocytes. J. Immunother. 35: 400-408.
149. Inderberg-Suso, E. M., S. Trachsel, K. Lislerud, A. M. Rasmussen, and G. Gaudernack. 2012. Widespread CD4+ T-cell reactivity to novel hTERT epitopes following vaccination of cancer patients with a single hTERT peptide GV1001. OncoImmunology 1: 670-686.
150. McKinney, D. M., S. Southwood, D. Hinz, C. Oseroff, C. S. Arlehamn, V. Schulten, R. Taplitz, D. Broide, W. A. Hanekom, T. J. Scriba, et al. 2013. A strategy to determine HLA class II restriction broadly covering the DR, DP, and DQ allelic variants most commonly expressed in the general population. Immunogenetics 65: 357-370.
151. Greenbaum, J., J. Sidney, J. Chung, C. Brander, B. Peters, and A. Sette. 2011. Functional classification of class II human leukocyte antigen (HLA) molecules reveals seven different supertypes and a surprising degree of repertoire sharing across supertypes. Immunogenetics 63: 325-335.
152. Bos, R., and L. A. Sherman. 2010. CD4+ T-cell help in the tumor milieu is required for recruitment and cytolytic function of CD8+ T lymphocytes. Cancer Res. 70: 8368-8377.
153. Pardoll, D. M. 1999. Inducing autoimmune disease to treat cancer. Proc. Natl. Acad. Sci. USA 96: 5340-5342.
154. Dudley, M. E., J. R. Wunderlich, P. F. Robbins, J. C. Yang, P. Hwu, D. J. Schwartzentruber, S. L. Topalian, R. Sherry, N. P. Restifo, A. M. Hubicki, et al. 2002. Cancer regression and autoimmunity in patients after clonal repopulation with antitumor lymphocytes. Science 298: 850-854.
155. U.S. Food and Drug Administration. Paving the Way for Personalized Medicine: FDA's Role in a New Era of Medical Product Development. Available at: http://www.fda.gov/downloads/ScienceResearch/SpecialTopics/PersonalizedMedicine/UCM372421.pdf. Accessed: November 2014.