At the Bedside: CTLA-4- and PD-1-blocking antibodies in cancer immunotherapy

Journal of Leukocyte Biology

Volumn 94, Issue 1, 2013, Pages 41-53

  Callahan, Margaret K ^a,b   Wolchok, Jedd D ^a,b,c  

^a MEMORIAL SLOAN KETTERING CANCER CENTER   (United States)

^b WEILL CORNELL MEDICAL COLLEGE   (United States)

^c LUDWIG INSTITUTE FOR CANCER RESEARCH   (Australia)

Author keywords

Endpoints; Overall survival; Tumor

Indexed keywords

AMP 224; ANTIBODY; BMS 936559; CORTICOSTEROID; CYTOTOXIC T LYMPHOCYTE ANTIGEN 4 ANTIBODY; DACARBAZINE; GLYCOPROTEIN GP 100; GRANULOCYTE MACROPHAGE COLONY STIMULATING FACTOR VACCINE; IMMUNOSUPPRESSIVE AGENT; IPILIMUMAB; LIVER ENZYME; MEDI 4736; MK 3475; MPDL 3280A; MYCOPHENOLIC ACID 2 MORPHOLINOETHYL ESTER; NIVOLUMAB; PEPTIDE VACCINE; PHARMACOLOGICAL BIOMARKER; PIDILIZUMAB; PLACEBO; PROGRAMMED DEATH 1 LIGAND 1; PROGRAMMED DEATH 1 LIGAND 1 ANTIBODY; PROGRAMMED DEATH 1 RECEPTOR; PROGRAMMED DEATH 1 RECEPTOR ANTIBODY; RG 7446; SIPULEUCEL T; TEMOZOLOMIDE; TICILIMUMAB; TUMOR ANTIGEN; TUMOR NECROSIS FACTOR ANTIBODY; UNCLASSIFIED DRUG; UNINDEXED DRUG;

ADOPTIVE TRANSFER; ADRENAL INSUFFICIENCY; ANDROGEN DEPRIVATION THERAPY; ARTHRALGIA; ARTICLE; BREAST CANCER; CANCER COMBINATION CHEMOTHERAPY; CANCER GROWTH; CANCER IMMUNOTHERAPY; CANCER SURVIVAL; CHEMORADIOTHERAPY; COLITIS; COLORECTAL CANCER; CONJUNCTIVITIS; CYTOPENIA; DERMATITIS; DIARRHEA; DOSE RESPONSE; DRUG APPROVAL; DRUG DOSE COMPARISON; DRUG DOSE ESCALATION; DRUG EFFICACY; DRUG HALF LIFE; DRUG WITHDRAWAL; HEMATOLOGIC MALIGNANCY; HEPATITIS; HUMAN; HYPOPHYSIS DISEASE; HYPOPHYSITIS; HYPOTHYROIDISM; IMMUNOMODULATION; INOPERABLE CANCER; KIDNEY CARCINOMA; LUNG NON SMALL CELL CANCER; MELANOMA; MELANOMA B16; METASTATIC MELANOMA; MYOPATHY; NEPHRITIS; NEUROPATHY; NONHUMAN; OVARY CANCER; OVERALL SURVIVAL; PANCREAS CANCER; PANCREATITIS; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); PNEUMONIA; PRIORITY JOURNAL; PROSTATE CANCER; PROTEIN EXPRESSION; PRURITUS; RANDOMIZED CONTROLLED TRIAL (TOPIC); RASH; SIDE EFFECT; SINGLE DRUG DOSE; SOLID TUMOR; STOMACH CANCER; T LYMPHOCYTE; THYROIDITIS; TOXICITY TESTING; TUMOR ESCAPE; TUMOR VOLUME; UVEITIS; VITILIGO;

ENDPOINTS; OVERALL SURVIVAL; TUMOR;

ANTIBODIES, BLOCKING; CLINICAL TRIALS AS TOPIC; CTLA-4 ANTIGEN; HUMANS; IMMUNOTHERAPY; NEOPLASMS; PROGRAMMED CELL DEATH 1 RECEPTOR;

EID: 84879599112     PISSN: 07415400     EISSN: 19383673     Source Type: Journal    
DOI: 10.1189/jlb.1212631     Document Type: Article

References (116)

1. Baxter, A. G., Hodgkin, P. D. (2002) Activation rules: the two-signal theories of immune activation. Nat. Rev. Immunol. 2, 439-446.
2. Jenkins, M. K., Schwartz, R. H. (1987) Antigen presentation by chemically modified splenocytes induces antigen-specific T cell unresponsiveness in vitro and in vivo. J. Exp. Med. 165, 302-319.
3. Lafferty, K. J., Cunningham, A. J. (1975) A new analysis of allogeneic interactions. Aust. J. Exp. Biol. Med. Sci. 53, 27-42.
4. Bretscher, P., Cohn, M. (1970) A theory of self-nonself discrimination. Science 169, 1042-1049.
5. Dunn, G. P., Old, L. J., Schreiber, R. D. (2004) The three Es of cancer immunoediting. Annu. Rev. Immunol. 22, 329-360.
6. Peggs, K. S., Quezada, S. A., Allison, J. P. (2009) Cancer immunotherapy: co-stimulatory agonists and co-inhibitory antagonists. Clin. Exp. Immunol. 157, 9-19.
7. Leach, D. R., Krummel, M. F., Allison, J. P. (1996) Enhancement of antitumor immunity by CTLA-4 blockade. Science 271, 1734-1736.
8. Kwon, E. D., Hurwitz, A. A., Foster, B. A., Madias, C., Feldhaus, A. L., Greenberg, N. M., Burg, M. B., Allison, J. P. (1997) Manipulation of T cell costimulatory and inhibitory signals for immunotherapy of prostate cancer. Proc. Natl. Acad. Sci. USA 94, 8099-8103.
9. Yang, Y. F., Zou, J. P., Mu, J., Wijesuriya, R., Ono, S., Walunas, T., Bluestone, J., Fujiwara, H., Hamaoka, T. (1997) Enhanced induction of antitumor T-cell responses by cytotoxic T lymphocyte-associated molecule-4 blockade: the effect is manifested only at the restricted tumorbearing stages. Cancer Res. 57, 4036-4041.
10. Shrikant, P., Khoruts, A., Mescher, M. F. (1999) CTLA-4 blockade reverses CD8+ T cell tolerance to tumor by a CD4+ T cell-and IL-2-dependent mechanism. Immunity 11, 483-493.
11. Sotomayor, E. M., Borrello, I., Tubb, E., Allison, J. P., Levitsky, H. I. (1999) In vivo blockade of CTLA-4 enhances the priming of responsive T cells but fails to prevent the induction of tumor antigen-specific tolerance. Proc. Natl. Acad. Sci. USA 96, 11476-11481.
12. Allison, J. P., Hurwitz, A. A., Leach, D. R. (1995) Manipulation of costimulatory signals to enhance antitumor T-cell responses. Curr. Opin. Immunol. 7, 682-686.
13. Grosso, J. F., Kelleher, C. C., Harris, T. J., Maris, C. H., Hipkiss, E. L., De Marzo, A., Anders, R., Netto, G., Getnet, D., Bruno, T. C., Goldberg, M. V., Pardoll, D. M., Drake, C. G. (2007) LAG-3 regulates CD8+ T cell accumulation and effector function in murine self-and tumortolerance systems. J. Clin. Invest. 117, 3383-3392.
14. Hirano, F., Kaneko, K., Tamura, H., Dong, H., Wang, S., Ichikawa, M., Rietz, C., Flies, D. B., Lau, J. S., Zhu, G., Tamada, K., Chen, L. (2005) Blockade of B7-H1 and PD-1 by monoclonal antibodies potentiates cancer therapeutic immunity. Cancer Res. 65, 1089-1096.
15. Curiel, T. J., Wei, S., Dong, H., Alvarez, X., Cheng, P., Mottram, P., Krzysiek, R., Knutson, K. L., Daniel, B., Zimmermann, M. C., David, O., Burow, M., Gordon, A., Dhurandhar, N., Myers, L., Berggren, R., Hemminki, A., Alvarez, R. D., Emilie, D., Curiel, D. T., Chen, L., Zou, W. (2003) Blockade of B7-H1 improves myeloid dendritic cell-mediated antitumor immunity. Nat. Med. 9, 562-567.
16. Strome, S. E., Dong, H., Tamura, H., Voss, S. G., Flies, D. B., Tamada, K., Salomao, D., Cheville, J., Hirano, F., Lin, W., Kasperbauer, J. L., Ballman, K. V., Chen, L. (2003) B7-H1 blockade augments adoptive T-cell immunotherapy for squamous cell carcinoma. Cancer Res. 63, 6501-6505.
17. Iwai, Y., Ishida, M., Tanaka, Y., Okazaki, T., Honjo, T., Minato, N. (2002) Involvement of PD-L1 on tumor cells in the escape from host immune system and tumor immunotherapy by PD-L1 blockade. Proc. Natl. Acad. Sci. USA 99, 12293-12297.
18. Iwai, Y., Terawaki, S., Honjo, T. (2005) PD-1 blockade inhibits hematogenous spread of poorly immunogenic tumor cells by enhanced recruitment of effector T cells. Int. Immunol. 17, 133-144.
19. Radhakrishnan, S., Nguyen, L. T., Ciric, B., Flies, D., Van Keulen, V. P., Tamada, K., Chen, L., Rodriguez, M., Pease, L. R. (2004) Immunotherapeutic potential of B7-DC (PD-L2) cross-linking antibody in conferring antitumor immunity. Cancer Res. 64, 4965-4972.
20. Intlekofer, A. M., Thompson, C. B. At the bench: Preclinical rationale for CTLA-4 and PD-1 blockade as cancer immunotherapy. J. Leukoc. Biol. 94, 25-39.
21. Ishida, Y., Agata, Y., Shibahara, K., Honjo, T. (1992) Induced expression of PD-1, a novel member of the immunoglobulin gene superfamily, upon programmed cell death. EMBO J. 11, 3887-3895.
22. Tchekmedyian, S., et al. (2002) MDX-010 (human anti-CTLA4): a Phase I trial in malignant melanoma. Proc. Am. Soc. Clin. Oncol. 21
23. Wolchok, J.D., Neyns, B., Linette, G., Negrier, S., Lutzky, J., Thomas, L., Waterfield, W., Schadendorf, D., Smylie, M., Guthrie Jr., T., Grob, J.J., Chesney, J., Chin, K., Chen, K., Hoos, A., O'Day, S.J., Lebbe, C. (2010) Ipilimumab monotherapy in patients with pretreated advanced melanoma: a randomised, double-blind, multicentre, Phase II, doseranging study. Lancet Oncol. 11, 155-164.
24. Hodi, F. S., O'Day, S. J., McDermott, D. F., Weber, R. W., Sosman, J. A., Haanen, J. B., Gonzalez, R., Robert, C., Schadendorf, D., Hassel, J. C., Akerley, W., van den Eertwegh, A. J., Lutzky, J., Lorigan, P., Vaubel, J. M., Linette, G. P., Hogg, D., Ottensmeier, C. H., Lebbe, C., Peschel, C., Quirt, I., Clark, J. I., Wolchok, J. D., Weber, J. S., Tian, J., Yellin, M. J., Nichol, G. M., Hoos, A., Urba, W. J. (2010) Improved survival with ipilimumab in patients with metastatic melanoma. N. Engl. J. Med. 363, 711-723.
25. Robert, C., Thomas, L., Bondarenko, I., O'Day, S., M D, J. W., Garbe, C., Lebbe, C., Baurain, J. F., Testori, A., Grob, J. J., Davidson, N., Richards, J., Maio, M., Hauschild, A., Miller W. H., Jr., Gascon, P., Lotem, M., Harmankaya, K., Ibrahim, R., Francis, S., Chen, T. T., Humphrey, R., Hoos, A., Wolchok, J. D. (2011) Ipilimumab plus dacarbazine for previously untreated metastatic melanoma. N. Engl. J. Med. 364, 2517-2526.
26. Kirkwood, J. M., Lorigan, P., Hersey, P., Hauschild, A., Robert, C., McDermott, D., Marshall, M. A., Gomez-Navarro, J., Liang, J. Q., Bulanhagui, C. A. (2010) Phase II trial of tremelimumab (CP-675,206) in patients with advanced refractory or relapsed melanoma. Clin. Care Res. 16, 1042-1048.
27. Ribas, A., et al. (2008) Phase III, open-label, randomized, comparative study of tremelimumab (CP-675,206) and chemotherapy (temozolomide or dacarbazine) in patients with advanced melanoma. J. Clin. Oncol. 26 (Suppl.; abs. LBA9011).
28. Marshall, M. A., Ribas, A., Huang, B. (2010) Evaluation of baseline serum C-reactive protein (CRP) and benefit from tremelimumab compared to chemotherapy in first-line melanoma. J. Clin. Oncol. 28 (Suppl; abs. 2609).
29. Wolchok, J. D., Hoos, A., O'Day, S., Weber, J. S., Hamid, O., Lebbe, C., Maio, M., Binder, M., Bohnsack, O., Nichol, G., Humphrey, R., Hodi, F. S. (2009) Guidelines for the evaluation of immune therapy activity in solid tumors: immune-related response criteria. Clin. Care Res. 15, 7412-7420.
30. Topalian, S. L., Hodi, F. S., Brahmer, J. R., Gettinger, S. N., Smith, D. C., McDermott, D. F., Powderly, J. D., Carvajal, R. D., Sosman, J. A., Atkins, M. B., Leming, P. D., Spigel, D. R., Antonia, S. J., Horn, L., Drake, C. G., Pardoll, D. M., Chen, L., Sharfman, W. H., Anders, R. A., Taube, J. M., McMiller, T. L., Xu, H., Korman, A. J., Jure-Kunkel, M., Agrawal, S., McDonald, D., Kollia, G. D., Gupta, A., Wigginton, J. M., Sznol, M. (2012) Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N. Engl. J. Med. 366, 2443-2454.
31. Brahmer, J. R., Tykodi, S. S., Chow, L. Q., Hwu, W. J., Topalian, S. L., Hwu, P., Drake, C. G., Camacho, L. H., Kauh, J., Odunsi, K., Pitot, H. C., Hamid, O., Bhatia, S., Martins, R., Eaton, K., Chen, S., Salay, T. M., Alaparthy, S., Grosso, J. F., Korman, A. J., Parker, S. M., Agrawal, S., Goldberg, S. M., Pardoll, D. M., Gupta, A., Wigginton, J. M. (2012) Safety and activity of anti-PD-L1 antibody in patients with advanced cancer. N. Engl. J. Med. 366, 2455-2465.
32. Weber, J. (2009) Ipilimumab: controversies in its development, utility and autoimmune adverse events. Cancer Immunol. Immunother. 58, 823-830.
33. Di Giacomo, A. M., Biagioli, M., Maio, M. (2010) The emerging toxicity profiles of anti-CTLA-4 antibodies across clinical indications. Semin. Oncol. 37, 499-507.
34. Forde, P.M., Rock, K., Wilson, G., O'Byrne, K. J. (2012) Ipilimumabinduced immune-related renal failure-a case report. Anticancer Res. 32, 4607-4608.
35. Maur, M., Tomasello, C., Frassoldati, A., Dieci, M. V., Barbieri, E., Conte, P. (2012) Posterior reversible encephalopathy syndrome during ipilimumab therapy for malignant melanoma. J. Clin. Oncol. 30, e76-e78.
36. Andrews, S., Holden, R. (2012) Characteristics and management of immunerelated adverse effects associated with ipilimumab, a new immunotherapy for metastatic melanoma. Cancer Manag. Res. 4, 299-307.
37. Beck, K. E., Blansfield, J. A., Tran, K. Q., Feldman, A. L., Hughes, M. S., Royal, R. E., Kammula, U. S., Topalian, S. L., Sherry, R. M., Kleiner, D., Quezado, M., Lowy, I., Yellin, M., Rosenberg, S. A., Yang, J. C. (2006) Enterocolitis in patients with cancer after antibody blockade of cytotoxic T-lymphocyte-associated antigen 4. J. Clin. Oncol. 24, 2283-2289.
38. Wolchok, J. (2012) How recent advances in immunotherapy are changing the standard of care for patients with metastatic melanoma. Ann. Oncol. 23 (Suppl. 8), viii15-viii21.
39. Juszczak, A., Gupta, A., Karavitaki, N., Middleton, M. R., Grossman, A. B. (2012) Ipilimumab: a novel immunomodulating therapy causing autoimmune hypophysitis: a case report and review. Eur. J. Endocrinol. 167, 1-5.
40. Dillard, T., Yedinak, C. G., Alumkal, J., Fleseriu, M. (2010) Anti-CTLA-4 antibody therapy associated autoimmune hypophysitis: serious immune related adverse events across a spectrum of cancer subtypes. Pituitary 13, 29-38.
41. Kaehler, K. C., Egberts, F., Lorigan, P., Hauschild, A. (2009) Anti-CTLA-4 therapy-related autoimmune hypophysitis in a melanoma patient. Melanoma Res. 19, 333-334.
42. Peggs, K. S., Quezada, S. A., Allison, J. P. (2008) Cell intrinsic mechanisms of T-cell inhibition and application to cancer therapy. Immunol. Rev. 224, 141-165.
43. van Elsas, A., Hurwitz, A. A., Allison, J. P. (1999) Combination immunotherapy of B16 melanoma using anti-cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) and granulocyte/macrophage colony-stimulating factor (GM-CSF)-producing vaccines induces rejection of subcutaneous and metastatic tumors accompanied by autoimmune depigmentation. J. Exp. Med. 190, 355-366.
44. Hurwitz, A. A., Sullivan, T. J., Krummel, M. F., Sobel, R. A., Allison, J. P. (1997) Specific blockade of CTLA-4/B7 interactions results in exacerbated clinical and histologic disease in an actively-induced model of experimental allergic encephalomyelitis. J. Neuroimmunol. 73, 57-62.
45. Kantoff, P. W., Higano, C. S., Shore, N. D., Berger, E. R., Small, E. J., Penson, D. F., Redfern, C. H., Ferrari, A. C., Dreicer, R., Sims, R. B., Xu, Y., Frohlich, M. W., Schellhammer, P. F. (2010) Sipuleucel-T immunotherapy for castration-resistant prostate cancer. N. Engl. J. Med. 363, 411-422.
46. Small, E. J., Schellhammer, P. F., Higano, C. S., Redfern, C. H., Nemunaitis, J. J., Valone, F. H., Verjee, S. S., Jones, L. A., Hershberg, R. M. (2006) Placebo-controlled Phase III trial of immunologic therapy with sipuleucel-T (APC8015) in patients with metastatic, asymptomatic hormone refractory prostate cancer. J. Clin. Oncol. 24, 3089-3094.
47. Kantoff, P. W., Schuetz, T. J., Blumenstein, B. A., Glode, L. M., Bilhartz, D. L., Wyand, M., Manson, K., Panicali, D. L., Laus, R., Schlom, J., Dahut, W. L., Arlen, P. M., Gulley, J. L., Godfrey, W. R. (2010) Overall survival analysis of a Phase II randomized controlled trial of a poxviral-based PSA-targeted immunotherapy in metastatic castrationresistant prostate cancer. J. Clin. Oncol. 28, 1099-1105.
48. Prieto, P. A., Yang, J. C., Sherry, R. M., Hughes, M. S., Kammula, U. S., White, D. E., Levy, C. L., Rosenberg, S. A., Phan, G. Q. (2012) CTLA-4 blockade with ipilimumab: long-term follow-up of 177 patients with metastatic melanoma. Clin. Cancer Res. 18, 2039-2047.
49. Postow, M. A., Callahan, M. K., Wolchok, J. D. (2012) The antitumor immunity of ipilimumab: (T-cell) memories to last a lifetime? Clin. Cancer Res. 18, 1821-1823.
50. Yamazaki, T., Akiba, H., Iwai, H., Matsuda, H., Aoki, M., Tanno, Y., Shin, T., Tsuchiya, H., Pardoll, D. M., Okumura, K., Azuma, M., Yagita, H. (2002) Expression of programmed death 1 ligands by murine T cells and APC. J. Immunol. 169, 5538-5545.
51. Eppihimer, M. J., Gunn, J., Freeman, G. J., Greenfield, E. A., Chenova, T., Erickson, J., Leonard, J. P. (2002) Expression and regulation of the PD-L1 immunoinhibitory molecule on microvascular endothelial cells. Microcirculation 9, 133-145.
52. Schreiner, B., Mitsdoerffer, M., Kieseier, B. C., Chen, L., Hartung, H. P., Weller, M., Wiendl, H. (2004) Interferon-β enhances monocyte and dendritic cell expression of B7-H1 (PD-L1), a strong inhibitor of autologous T-cell activation: relevance for the immune modulatory effect in multiple sclerosis. J. Neuroimmunol. 155, 172-182.
53. Lee, S. J., Jang, B. C., Lee, S. W., Yang, Y. I., Suh, S. I., Park, Y. M., Oh, S., Shin, J. G., Yao, S., Chen, L., Choi, I. H. (2006) Interferon regulatory factor-1 is prerequisite to the constitutive expression and IFN-β-induced upregulation of B7-H1 (CD274). FEBS Lett. 580, 755-762.
54. Liu, J., Hamrouni, A., Wolowiec, D., Coiteux, V., Kuliczkowski, K., Hetuin, D., Saudemont, A., Quesnel, B. (2007) Plasma cells from multiple myeloma patients express B7-H1 (PD-L1) and increase expression after stimulation with IFN-{γ} and TLR ligands via a MyD88-, TRAF6-, and MEK-dependent pathway. Blood 110, 296-304.
55. Thompson, R. H., Gillett, M. D., Cheville, J. C., Lohse, C. M., Dong, H., Webster, W. S., Chen, L., Zincke, H., Blute, M. L., Leibovich, B. C., Kwon, E. D. (2005) Costimulatory molecule B7-H1 in primary and metastatic clear cell renal cell carcinoma. Cancer 104, 2084-2091.
56. Thompson, R. H., Gillett, M. D., Cheville, J. C., Lohse, C. M., Dong, H., Webster, W. S., Krejci, K. G., Lobo, J. R., Sengupta, S., Chen, L., Zincke, H., Blute, M. L., Strome, S. E., Leibovich, B. C., Kwon, E. D. (2004) Costimulatory B7-H1 in renal cell carcinoma patients: indicator of tumor aggressiveness and potential therapeutic target. Proc. Natl. Acad. Sci. USA 101, 17174-17179.
57. Inman, B. A., Sebo, T. J., Frigola, X., Dong, H., Bergstralh, E. J., Frank, I., Fradet, Y., Lacombe, L., Kwon, E. D. (2007) PD-L1 (B7-H1) expression by urothelial carcinoma of the bladder and BCG-induced granulomata: associations with localized stage progression. Cancer 109, 1499-1505.
58. Nakanishi, J., Wada, Y., Matsumoto, K., Azuma, M., Kikuchi, K., Ueda, S. (2007) Overexpression of B7-H1 (PD-L1) significantly associates with tumor grade and postoperative prognosis in human urothelial cancers. Cancer Immunol. Immunother. 56, 1173-1182.
59. Hamanishi, J., Mandai, M., Iwasaki, M., Okazaki, T., Tanaka, Y., Yamaguchi, K., Higuchi, T., Yagi, H., Takakura, K., Minato, N., Honjo, T., Fujii, S. (2007) Programmed cell death 1 ligand 1 and tumor-infiltrating CD8+ T lymphocytes are prognostic factors of human ovarian cancer. Proc. Natl. Acad. Sci. USA 104, 3360-3365.
60. Nomi, T., Sho, M., Akahori, T., Hamada, K., Kubo, A., Kanehiro, H., Nakamura, S., Enomoto, K., Yagita, H., Azuma, M., Nakajima, Y. (2007) Clinical significance and therapeutic potential of the programmed death-1 ligand/programmed death-1 pathway in human pancreatic cancer. Clin. Cancer Res. 13, 2151-2157.
61. Wu, C., Zhu, Y., Jiang, J., Zhao, J., Zhang, X. G., Xu, N. (2006) Immunohistochemical localization of programmed death-1 ligand-1 (PD-L1) in gastric carcinoma and its clinical significance. Acta Histochem. 108, 19-24.
62. Dong, H., Strome, S. E., Salomao, D. R., Tamura, H., Hirano, F., Flies, D. B., Roche, P. C., Lu, J., Zhu, G., Tamada, K., Lennon, V. A., Celis, E., Chen, L. (2002) Tumor-associated B7-H1 promotes T-cell apoptosis: a potential mechanism of immune evasion. Nat. Med. 8, 793-800.
63. Wintterle, S., Schreiner, B., Mitsdoerffer, M., Schneider, D., Chen, L., Meyermann, R., Weller, M., Wiendl, H. (2003) Expression of the B7-related molecule B7-H1 by glioma cells: a potential mechanism of immune paralysis. Cancer Res. 63, 7462-7467.
64. Brown, J. A., Dorfman, D. M., Ma, F. R., Sullivan, E. L., Munoz, O., Wood, C. R., Greenfield, E. A., Freeman, G. J. (2003) Blockade of programmed death-1 ligands on dendritic cells enhances T cell activation and cytokine production. J. Immunol. 170, 1257-1266.
65. Thompson, R. H., Kuntz, S. M., Leibovich, B. C., Dong, H., Lohse, C. M., Webster, W. S., Sengupta, S., Frank, I., Parker, A. S., Zincke, H., Blute, M. L., Sebo, T. J., Cheville, J. C., Kwon, E. D. (2006) Tumor B7-H1 is associated with poor prognosis in renal cell carcinoma patients with long-term follow-up. Cancer Res. 66, 3381-3385.
66. Konishi, J., Yamazaki, K., Azuma, M., Kinoshita, I., Dosaka-Akita, H., Nishimura, M. (2004) B7-H1 expression on non-small cell lung cancer cells and its relationship with tumor-infiltrating lymphocytes and their PD-1 expression. Clin. Cancer Res. 10, 5094-5100.
67. Xerri, L., Chetaille, B., Serriari, N., Attias, C., Guillaume, Y., Arnoulet, C., Olive, D. (2008) Programmed death 1 is a marker of angioimmunoblastic T-cell lymphoma and B-cell small lymphocytic lymphoma/ chronic lymphocytic leukemia. Hum. Pathol. 39, 1050-1058.
68. Dorfman, D. M., Brown, J. A., Shahsafaei, A., Freeman, G. J. (2006) Programmed death-1 (PD-1) is a marker of germinal center-associated T cells and angioimmunoblastic T-cell lymphoma. Am. J. Surg. Pathol. 30, 802-810.
69. Rosenwald, A., Wright, G., Leroy, K., Yu, X., Gaulard, P., Gascoyne, R. D., Chan, W. C., Zhao, T., Haioun, C., Greiner, T. C., et al. (2003) Molecular diagnosis of primary mediastinal B cell lymphoma identifies a clinically favorable subgroup of diffuse large B cell lymphoma related to Hodgkin lymphoma. J. Exp. Med. 198, 851-862.
70. Tamura, H., Dan, K., Tamada, K., Nakamura, K., Shioi, Y., Hyodo, H., Wang, S. D., Dong, H., Chen, L., Ogata, K. (2005) Expression of functional B7-H2 and B7.2 costimulatory molecules and their prognostic implications in de novo acute myeloid leukemia. Clin. Cancer Res. 11, 5708-5717.
71. Thompson, R. H., Webster, W. S., Cheville, J. C., Lohse, C. M., Dong, H., Leibovich, B. C., Kuntz, S. M., Sengupta, S., Kwon, E. D., Blute, M. L. (2005) B7-H1 glycoprotein blockade: a novel strategy to enhance immunotherapy in patients with renal cell carcinoma. Urology 66, 10-14.
72. Wong, R. M., Scotland, R. R., Lau, R. L., Wang, C., Korman, A. J., Kast, W. M., Weber, J. S. (2007) Programmed death-1 blockade enhances expansion and functional capacity of human melanoma antigen-specific CTLs. Int. Immunol. 19, 1223-1234.
73. Fourcade, J., Kudela, P., Sun, Z., Shen, H., Land, S. R., Lenzner, D., Guillaume, P., Luescher, I. F., Sander, C., Ferrone, S., Kirkwood, J. M., Zarour, H. M. (2009) PD-1 is a regulator of NY-ESO-1-specific CD8+ T cell expansion in melanoma patients. J. Immunol. 182, 5240-5249.
74. Matsuzaki, J., Gnjatic, S., Mhawech-Fauceglia, P., Beck, A., Miller, A., Tsuji, T., Eppolito, C., Qian, F., Lele, S., Shrikant, P., Old, L. J., Odunsi, K. (2010) Tumor-infiltrating NY-ESO-1-specific CD8+ T cells are negatively regulated by LAG-3 and PD-1 in human ovarian cancer. Proc. Natl. Acad. Sci. USA 107, 7875-7880.
75. Ahmadzadeh, M., Johnson, L. A., Heemskerk, B., Wunderlich, J. R., Dudley, M. E., White, D. E., Rosenberg, S. A. (2009) Tumor antigenspecific CD8 T cells infiltrating the tumor express high levels of PD-1 and are functionally impaired. Blood 114, 1537-1544.
76. Dong, H., Zhu, G., Tamada, K., Chen, L. (1999) B7-H1, a third member of the B7 family, co-stimulates T-cell proliferation and interleukin-10 secretion. Nat. Med. 5, 1365-1369.
77. Freeman, G. J., Long, A. J., Iwai, Y., Bourque, K., Chernova, T., Nishimura, H., Fitz, L. J., Malenkovich, N., Okazaki, T., Byrne, M. C., Horton, H. F., Fouser, L., Carter, L., Ling, V., Bowman, M. R., Carreno, B. M., Collins, M., Wood, C. R., Honjo, T. (2000) Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation. J. Exp. Med. 192, 1027-1034.
78. Berger, R., Rotem-Yehudar, R., Slama, G., Landes, S., Kneller, A., Leiba, M., Koren-Michowitz, M., Shimoni, A., Nagler, A. (2008) Phase I safety and pharmacokinetic study of CT-011, a humanized antibody interacting with PD-1, in patients with advanced hematologic malignancies. Clin. Cancer Res. 14, 3044-3051.
79. Sosman, J., Sznol, M., McDermott, D., Carvsjal, R. Lawrence, D. Topalian, S. L. Wigginton, J. M. Kollia, G. Gupta A. Hodi, F. (2012) Clinical activity and safety of anti-programmed death-1 (PD-1) (BMS-936558/ MDX-1106/ONO-4538) in patients (PTS) with advanced melanoma (MEL) in ESMO.
80. Patnaik, A., Kang, S. P., Tolcher, A. W., Rasco, D. W., Papadopoulos, K. P., Beeram, M., Drengler, R., Chen, C., Smith, L., Perez, C., Gergich, K. (2012) Phase I study of MK-3475 (anti-PD-1 monoclonal antibody) in patients with advanced solid tumors. J. Clin. Oncol. 30 (Suppl.; abs. 2512).
81. Hamid, O. (2012) Efficacy and Safety of MK-3475 in Patients with Advanced Melanoma in Society for Melanoma Research. 2012 Congress, Hollywood, CA, USA.
82. Chen, D. S., Irving, B. A., Hodi, F. S. (2012) Molecular pathways: nextgeneration immunotherapy-inhibiting programmed death-ligand 1 and programmed death-1. Clin. Cancer Res. 18, 6580-6587.
83. Berman, D., et al. (2009) Association of peripheral blood absolute lymphocyte count (ALC) and clinical activity in patients (pts) with advanced melanoma treated with ipilimumab. J. Clin. Oncol. 27, 3020 (abs.).
84. Ku, G. Y., Yuan, J., Page, D. B., Schroeder, S. E., Panageas, K. S., Carvajal, R. D., Chapman, P. B., Schwartz, G. K., Allison, J. P., Wolchok, J. D. (2010) Single-institution experience with ipilimumab in advanced melanoma patients in the compassionate use setting: lymphocyte count after 2 doses correlates with survival. Cancer 116, 1767-1775.
85. Yang, R. K. (2010) CTLA-4 blockade with ipilimumab increases peripheral CD8+ T cells: correlation with clinical outcomes. J. Clin. Oncol. 28, 2555 (abs.).
86. Yuan, J., Gnjatic, S., Li, H., Powel, S., Gallardo, H. F., Ritter, E., Ku, G. Y., Jungbluth, A. A., Segal, N. H., Rasalan, T. S., Manukian, G., Xu, Y., Roman, R. A., Terzulli, S. L., Heywood, M., Pogoriler, E., Ritter, G., Old, L. J., Allison, J. P., Wolchok, J. D. (2008) CTLA-4 blockade enhances polyfunctional NY-ESO-1 specific T cell responses in metastatic melanoma patients with clinical benefit. Proc. Natl. Acad. Sci. USA 105, 20410-20415.
87. Yuan, J., Adamow, M., Ginsberg, B. A., Rasalan, T. S., Ritter, E., Gallardo, H. F., Xu, Y., Pogoriler, E., Terzulli, S. L., Kuk, D., Panageas, K. S., Ritter, G., Sznol, M., Halaban, R., Jungbluth, A. A., Allison, J. P., Old, L. J., Wolchok, J. D., Gnjatic, S. (2011) Integrated NY-ESO-1 antibody and CD8+ T-cell responses correlate with clinical benefit in advanced melanoma patients treated with ipilimumab. Proc. Natl. Acad. Sci. USA 108, 16723-16728.
88. Goff, S. L., Robbins, P. F., El-Gamil, M., Rosenberg, S. A. (2009) No correlation between clinical response to CTLA-4 blockade and presence of NY-ESO-1 antibody in patients with metastatic melanoma. J. Immunother. 32, 884-885.
89. Burmeister, Y., Lischke, T., Dahler, A. C., Mages, H. W., Lam, K. P., Coyle, A. J., Kroczek, R. A., Hutloff, A. (2008) ICOS controls the pool size of effector-memory and regulatory T cells. J. Immunol. 180, 774-782.
90. Liakou, C. I., Kamat, A., Tang, D. N., Chen, H., Sun, J., Troncoso, P., Logothetis, C., Sharma, P. (2008) CTLA-4 blockade increases IFNγ-producing CD4+ICOShi cells to shift the ratio of effector to regulatory T cells in cancer patients. Proc. Natl. Acad. Sci. USA 105, 14987-14992.
91. Chen, H., Liakou, C. I., Kamat, A., Pettaway, C., Ward, J. F., Tang, D. N., Sun, J., Jungbluth, A. A., Troncoso, P., Logothetis, C., Sharma, P. (2009) Anti-CTLA-4 therapy results in higher CD4+ICOShi T cell frequency and IFN-β levels in both nonmalignant and malignant prostate tissues. Proc. Natl. Acad. Sci. USA 106, 2729-2734.
92. Vonderheide, R. H., LoRusso, P. M., Khalil, M., Gartner, E. M., Khaira, D., Soulieres, D., Dorazio, P., Trosko, J. A., Ruter, J., Mariani, G. L., Usari, T., Domchek, S. M. (2010) Tremelimumab in combination with exemestane in patients with advanced breast cancer and treatmentassociated modulation of inducible costimulator expression on patient T cells. Clin. Cancer Res. 16, 3485-3494.
93. Carthon, B. C., Wolchok, J. D., Yuan, J., Kamat, A., Ng Tang, D. S., Sun, J., Ku, G., Troncoso, P., Logothetis, C. J., Allison, J. P., Sharma, P. (2010) Preoperative CTLA-4 blockade: tolerability and immune monitoring in the setting of a presurgical clinical trial. Clin. Cancer Res. 16, 2861-2871.
94. Gajewski, T. F., Fuertes, M., Spaapen, R., Zheng, Y., Kline, J. (2011) Molecular profiling to identify relevant immune resistance mechanisms in the tumor microenvironment. Curr. Opin. Immunol. 23, 286-292.
95. Hamid, O., Schmidt, H., Nissan, A., Ridolfi, L., Aamdal, S., Hansson, J., Guida, M., Hyams, D. M., Gomez, H., Bastholt, L., Chasalow, S. D., Berman, D. (2011) A prospective Phase II trial exploring the association between tumor microenvironment biomarkers and clinical activity of ipilimumab in advanced melanoma. J. Transl. Med. 9, 204.
96. Ji, R. R., Chasalow, S. D., Wang, L., Hamid, O., Schmidt, H., Cogswell, J., Alaparthy, S., Berman, D., Jure-Kunkel, M., Siemers, N. O., Jackson, J. R., Shahabi, V. (2012) An immune-active tumor microenvironment favors clinical response to ipilimumab. Cancer Immunol. Immunother. 61, 1019-1031.
97. Taube, J. M., Anders, R. A., Young, G. D., Xu, H., Sharma, R., McMiller, T. L., Chen, S., Klein, A. P., Pardoll, D. M., Topalian, S. L., Chen, L. (2012) Colocalization of inflammatory response with B7-h1 expression in human melanocytic lesions supports an adaptive resistance mechanism of immune escape. Sci. Transl. Med. 4, 127ra37.
98. Grosso, J. F., Jure-Kunkel, M. N. (2013) CTLA-4 blockade in tumor models: an overview of preclinical and translational research. Cancer Immun. 13, 5.
99. Fong, L., Kwek, S. S., O'Brien, S., Kavanagh, B., McNeel, D. G., Weinberg, V., Lin, A. M., Rosenberg, J., Ryan, C. J., Rini, B. I., Small, E. J. (2009) Potentiating endogenous antitumor immunity to prostate cancer through combination immunotherapy with CTLA4 blockade and GM-CSF. Cancer Res. 69, 609-615.
100. Slovin, S. F., Beer, T. M., Higano, C. S., Tejwani, S., Hamid, O., Picus, J., Harzstark, A., Scher, H. I., Lan, Z., Lowy, I. (2009) Initial Phase II experience of ipilimumab (IPI) alone and in combination with radiotherapy (XRT) in patients with metastatic castration-resistant prostate cancer (mCRPC). J. Clin. Oncol. 27 (Suppl.), 15s (abs. 5138).
101. Mohebtash, M., Madan, R. A., Arlen, P. M., Rauckhorst, M., Tsang, K. Y., Cereda, V., Vergati, M., Poole, D. J., Dahut, W. L., Schlom, J., Gulley, J. L. (2009) Phase I trial of targeted therapy with PSA-TRICOM vaccine (V) and ipilimumab (ipi) in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC). J. Clin. Oncol. 27 (Suppl.), 15s (abs. 5138).
102. Small, E. J., Tchekmedyian, N. S., Rini, B. I., Fong, L., Lowy, I., Allison, J. P. (2007) A pilot trial of CTLA-4 blockade with human anti-CTLA-4 in patients with hormone-refractory prostate cancer. Clin. Cancer Res. 13, 1810-1815.
103. Lynch, T. J., Bondarenko, I. N., Luft, A., Serwatowski, P., Barlesi, F., Chacko, R. T., Sebastian, M., Siegel, J., Cuillerot, J., Reck, M. (2010) Phase II trial of ipilimumab (IPI) and paclitaxel/carboplatin (P/C) in first-line Stage IIIb/IV non-small cell lung cancer (NSCLC). J. Clin. Oncol. 28 (Suppl.), 15s (abs. 7531).
104. Yang, J. C., Hughes, M., Kammula, U., Royal, R., Sherry, R. M., Topalian, S. L., Suri, K. B., Levy, C., Allen, T., Mavroukakis, S., Lowy, I., White, D. E., Rosenberg, S. A. (2007) Ipilimumab (anti-CTLA4 antibody) causes regression of metastatic renal cell cancer associated with enteritis and hypophysitis. J. Immunother. 30, 825-830.
105. Royal, R. E., Levy, C., Turner, K., Mathur, A., Hughes, M., Kammula, U. S., Sherry, R. M., Topalian, S. L., Yang, J. C., Lowy, I., Rosenberg, S. A. (2010) Phase 2 trial of single agent ipilimumab (anti-CTLA-4) for locally advanced or metastatic pancreatic adenocarcinoma. J. Immunother. 33, 828-833.
106. Curran, M. A., Montalvo, W., Yagita, H., Allison, J. P. (2010) PD-1 and CTLA-4 combination blockade expands infiltrating T cells and reduces regulatory T and myeloid cells within B16 melanoma tumors. Proc. Natl. Acad. Sci. USA 107, 4275-4280.
107. Mangsbo, S. M., Sandin, L. C., Anger, K., Korman, A. J., Loskog, A., Totterman, T. H. (2010) Enhanced tumor eradication by combining CTLA-4 or PD-1 blockade with CpG therapy. J. Immunother. 33, 225-235.
108. Kroemer, G., Galluzzi, L., Kepp, O., Zitvogel, L. (2013) Immunogenic cell death in cancer therapy. Annu. Rev. Immunol. 31, 51-72.
109. Ma, Y., Conforti, R., Aymeric, L., Locher, C., Kepp, O., Kroemer, G., Zitvogel, L. (2011) How to improve the immunogenicity of chemotherapy and radiotherapy. Cancer Metastasis Rev. 30, 71-82.
110. Ma, Y., Kepp, O., Ghiringhelli, F., Apetoh, L., Aymeric, L., Locher, C., Tesniere, A., Martins, I., Ly, A., Haynes, N. M., Smyth, M. J., Kroemer, G., Zitvogel, L. (2010) Chemotherapy and radiotherapy: cryptic anticancer vaccines. Semin. Immunol. 22, 113-124.
111. Kroemer, G., Zitvogel, L. (2012) Abscopal but desirable: the contribution of immune responses to the efficacy of radiotherapy. Oncoimmunology 1, 407-408.
112. Dewan, M. Z., Galloway, A. E., Kawashima, N., Dewyngaert, J. K., Babb, J. S., Formenti, S. C., Demaria, S. (2009) Fractionated but not singledose radiotherapy induces an immune-mediated abscopal effect when combined with anti-CTLA-4 antibody. Clin. Cancer Res. 15, 5379-5388.
113. Demaria, S., Kawashima, N., Yang, A. M., Devitt, M. L., Babb, J. S., Allison, J. P., Formenti, S. C. (2005) Immune-mediated inhibition of metastases after treatment with local radiation and CTLA-4 blockade in a mouse model of breast cancer. Clin. Cancer Res. 11, 728-734.
114. Chakravarty, P. K., Alfieri, A., Thomas, E. K., Beri, V., Tanaka, K. E., Vikram, B., Guha, C. (1999) Flt3-ligand administration after radiation therapy prolongs survival in a murine model of metastatic lung cancer. Cancer Res. 59, 6028-6032.
115. Postow, M. A., Callahan, M. K., Barker, C. A., Yamada, Y., Yuan, J., Kitano, S., Mu, Z., Rasalan, T., Adamow, M., Ritter, E., Sedrak, C., Jungbluth, A. A., Chua, R., Yang, A. S., Roman, R. A., Rosner, S., Benson, B., Allison, J. P., Lesokhin, A. M., Gnjatic, S., Wolchok, J. D. (2012) Immunologic correlates of the abscopal effect in a patient with melanoma. N. Engl. J. Med. 366, 925-931.
116. Hiniker, S. M., Chen, D. S., Knox, S. J. (2012) Abscopal effect in a patient with melanoma. N. Engl. J. Med. 366, 2035.