CD27-mediated regulatory T cell depletion and effector T cell costimulation both contribute to antitumor efficacy

Journal of Immunology

Volumn 199, Issue 12, 2017, Pages 4110-4123

  Wasiuk, Anna ^a   Testa, James ^a   Weidlick, Jeff ^a   Sisson, Crystal ^a   Vitale, Laura ^a   Widger, Jenifer ^a   Crocker, Andrea ^a   Thomas, Lawrence J ^a   Goldstein, Joel ^a   Marsh, Henry C ^a   Keler, Tibor ^a   He, Li Zhen ^a  

^a Celldex Therapeutics Inc   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

CD27 ANTIGEN; FC RECEPTOR IIB; IMMUNOGLOBULIN G; VARLILUMAB; CD70 ANTIGEN; FC RECEPTOR; FCGR2B PROTEIN, MOUSE; IMMUNOGLOBULIN CLASS; IMMUNOLOGICAL ANTINEOPLASTIC AGENT; MONOCLONAL ANTIBODY;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANTINEOPLASTIC ACTIVITY; APOPTOSIS; ARTICLE; CONTROLLED STUDY; DRUG EFFICACY; DRUG POTENCY; DRUG TARGETING; EFFECTOR CELL; FEMALE; LYMPHOCYTE COUNT; LYMPHOCYTE DEPLETION; LYMPHOCYTE DIFFERENTIATION; MALE; MOUSE; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN PROTEIN INTERACTION; PROTEIN TARGETING; REGULATORY T LYMPHOCYTE; T LYMPHOCYTE ACTIVATION; TUMOR IMMUNITY; TUMOR MICROENVIRONMENT; AGONISTS; ANIMAL; ANTAGONISTS AND INHIBITORS; B CELL LYMPHOMA; BAGG ALBINO MOUSE; DRUG SCREENING; EXPERIMENTAL NEOPLASM; GERMFREE ANIMAL; HUMAN; IMMUNOLOGICAL MEMORY; IMMUNOLOGY; IMMUNOTHERAPY; METABOLISM; MISSENSE MUTATION; TRANSGENIC MOUSE;

ANIMALS; ANTIBODIES, MONOCLONAL; ANTINEOPLASTIC AGENTS, IMMUNOLOGICAL; APOPTOSIS; CD27 LIGAND; DRUG SCREENING ASSAYS, ANTITUMOR; FEMALE; HUMANS; IMMUNOGLOBULIN ISOTYPES; IMMUNOLOGIC MEMORY; IMMUNOTHERAPY; LYMPHOCYTE DEPLETION; LYMPHOMA, B-CELL; MICE; MICE, INBRED BALB C; MICE, TRANSGENIC; MUTATION, MISSENSE; NEOPLASMS, EXPERIMENTAL; RECEPTORS, IGG; SPECIFIC PATHOGEN-FREE ORGANISMS; T-LYMPHOCYTES, REGULATORY; TUMOR MICROENVIRONMENT; TUMOR NECROSIS FACTOR RECEPTOR SUPERFAMILY, MEMBER 7;

EID: 85038591414     PISSN: 00221767     EISSN: 15506606     Source Type: Journal    
DOI: 10.4049/jimmunol.1700606     Document Type: Article

References (63)

1. Wolchok, J. D., H. Kluger, M. K. Callahan, M. A. Postow, N. A. Rizvi, A. M. Lesokhin, N. H. Segal, C. E. Ariyan, R. A. Gordon, K. Reed, et al. 2013. Nivolumab plus ipilimumab in advanced melanoma. N. Engl. J. Med. 369: 122-133.
2. Ansell, S. M., A. M. Lesokhin, I. Borrello, A. Halwani, E. C. Scott, M. Gutierrez, S. J. Schuster, M. M. Millenson, D. Cattry, G. J. Freeman, et al. 2015. PD-1 blockade with nivolumab in relapsed or refractory Hodgkin's lymphoma. N. Engl. J. Med. 372: 311-319.
3. 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.
4. Hodi, F. S., S. J. O'Day, D. F. McDermott, R. W. Weber, J. A. Sosman, J. B. Haanen, R. Gonzalez, C. Robert, D. Schadendorf, J. C. Hassel, et al. 2010. Improved survival with ipilimumab in patients with metastatic melanoma. N. Engl. J. Med. 363: 711-723.
5. 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.
6. Melero, I., D. M. Berman, M. A. Aznar, A. J. Korman, J. L. Pérez Gracia, and J. Haanen. 2015. Evolving synergistic combinations of targeted immunotherapies to combat cancer. Nat. Rev. Cancer 15: 457-472.
7. Mahoney, K. M., P. D. Rennert, and G. J. Freeman. 2015. Combination cancer immunotherapy and new immunomodulatory targets. Nat. Rev. Drug Discov. 14: 561-584.
8. Simpson, T. R., F. Li, W. Montalvo-Ortiz, M. A. Sepulveda, K. Bergerhoff, F. Arce, C. Roddie, J. Y. Henry, H. Yagita, J. D. Wolchok, et al. 2013. Fc-dependent depletion of tumor-infiltrating regulatory T cells co-defines the efficacy of anti-CTLA-4 therapy against melanoma. J. Exp. Med. 210: 1695-1710.
9. Bulliard, Y., R. Jolicoeur, M. Windman, S. M. Rue, S. Ettenberg, D. A. Knee, N. S. Wilson, G. Dranoff, and J. L. Brogdon. 2013. Activating Fc g receptors contribute to the antitumor activities of immunoregulatory receptor-targeting antibodies. J. Exp. Med. 210: 1685-1693.
10. Bulliard, Y., R. Jolicoeur, J. Zhang, G. Dranoff, N. S. Wilson, and J. L. Brogdon. 2014. OX40 engagement depletes intratumoral Tregs via activating FcgRs, leading to antitumor efficacy. Immunol. Cell Biol. 92: 475-480.
11. Hintzen, R. Q., S. M. Lens, M. P. Beckmann, R. G. Goodwin, D. Lynch, and R. A. van Lier. 1994. Characterization of the human CD27 ligand, a novel member of the TNF gene family. J. Immunol. 152: 1762-1773.
12. Kawamura, T., Y. Ogawa, O. Shimozato, T. Ando, A. Nakao, T. Kobata, K. Okumura, H. Yagita, and S. Shimada. 2011. CD70 is selectively expressed on Th1 but not on Th2 cells and is required for Th1-type immune responses. J. Invest. Dermatol. 131: 1252-1261.
13. Tesselaar, K., L. A. Gravestein, G. M. van Schijndel, J. Borst, and R. A. van Lier. 1997. Characterization of murine CD70, the ligand of the TNF receptor family member CD27. J. Immunol. 159: 4959-4965.
14. Hintzen, R. Q., S. M. Lens, K. Lammers, H. Kuiper, M. P. Beckmann, and R. A. van Lier. 1995. Engagement of CD27 with its ligand CD70 provides a second signal for T cell activation. J. Immunol. 154: 2612-2623.
15. Taraban, V. Y., T. F. Rowley, D. F. Tough, and A. Al-Shamkhani. 2006. Requirement for CD70 in CD4+ Th cell-dependent and innate receptor-mediated CD8+ T cell priming. J. Immunol. 177: 2969-2975.
16. Keller, A. M., A. Schildknecht, Y. Xiao, M. van den Broek, and J. Borst. 2008. Expression of costimulatory ligand CD70 on steady-state dendritic cells breaks CD8+ T cell tolerance and permits effective immunity. Immunity 29: 934-946.
17. Keller, A. M., Y. Xiao, V. Peperzak, S. H. Naik, and J. Borst. 2009. Costimu-latory ligand CD70 allows induction of CD8+ T-cell immunity by immature dendritic cells in a vaccination setting. Blood 113: 5167-5175.
18. Bullock, T. N., and H. Yagita. 2005. Induction of CD70 on dendritic cells through CD40 or TLR stimulation contributes to the development of CD8+ T cell responses in the absence of CD4+ T cells. J. Immunol. 174: 710-717.
19. Ahrends, T., N. Babała, Y. Xiao, H. Yagita, H. van Eenennaam, and J. Borst. 2016. CD27 agonism plus PD-1 blockade recapitulates CD4+ T-cell help in therapeutic anticancer vaccination. Cancer Res. 76: 2921-2931.
20. Arens, R., K. Schepers, M. A. Nolte, M. F. van Oosterwijk, R. A. van Lier, T. N. Schumacher, and M. H. van Oers. 2004. Tumor rejection induced by CD70-mediated quantitative and qualitative effects on effector CD8+ T cell formation. J. Exp. Med. 199: 1595-1605.
21. Dong, H., N. A. Franklin, D. J. Roberts, H. Yagita, M. J. Glennie, and T. N. Bullock. 2012. CD27 stimulation promotes the frequency of IL-7 receptor-expressing memory precursors and prevents IL-12-mediated loss of CD8(+) T cell memory in the absence of CD4(+) T cell help. J. Immunol. 188: 3829-3838.
22. Hendriks, J., L. A. Gravestein, K. Tesselaar, R. A. van Lier, T. N. Schumacher, and J. Borst. 2000. CD27 is required for generation and long-term maintenance of T cell immunity. Nat. Immunol. 1: 433-440.
23. Hendriks, J., Y. Xiao, and J. Borst. 2003. CD27 promotes survival of activated T cells and complements CD28 in generation and establishment of the effector T cell pool. J. Exp. Med. 198: 1369-1380.
24. Schildknecht, A., I. Miescher, H. Yagita, and M. van den Broek. 2007. Priming of CD8+ T cell responses by pathogens typically depends on CD70-mediated interactions with dendritic cells. Eur. J. Immunol. 37: 716-728.
25. Welten, S. P., A. Redeker, K. L. Franken, C. A. Benedict, H. Yagita, F. M. Wensveen, J. Borst, C. J. Melief, R. A. van Lier, K. P. van Gisbergen, and R. Arens. 2013. CD27-CD70 costimulation controls T cell immunity during acute and persistent cytomegalovirus infection. J. Virol. 87: 6851-6865.
26. Alkhairy, O. K., R. Perez-Becker, G. J. Driessen, H. Abolhassani, J. van Montfrans, S. Borte, S. Choo, N. Wang, K. Tesselaar, M. Fang, et al. 2015. Novel mutations in TNFRSF7/CD27: clinical, immunologic, and genetic characterization of human CD27 deficiency. J. Allergy Clin. Immunol. 136: 703-712.e710.
27. Salzer, E., S. Daschkey, S. Choo, M. Gombert, E. Santos-Valente, S. Ginzel, M. Schwendinger, O. A. Haas, G. Fritsch, W. F. Pickl, et al. 2013. Combined immunodeficiency with life-threatening EBV-associated lymphoproliferative disorder in patients lacking functional CD27. Haematologica 98: 473-478.
28. van Montfrans, J. M., A. I. Hoepelman, S. Otto, M. van Gijn, L. van de Corput, R. A. de Weger, L. Monaco-Shawver, P. P. Banerjee, E. A. Sanders, C. M. Jol-van der Zijde, et al. 2012. CD27 deficiency is associated with combined immunodeficiency and persistent symptomatic EBV viremia. J. Allergy Clin. Immunol. 129: 787-793.e6
29. Abolhassani, H., E. S. Edwards, A. Ikinciogullari, H. Jing, S. Borte, M. Buggert, L. Du, M. Matsuda-Lennikov, R. Romano, R. Caridha, et al. 2017. Combined immunodeficiency and Epstein-Barr virus-induced B cell malignancy in humans with inherited CD70 deficiency. J. Exp. Med. 214: 91-106.
30. Izawa, K., E. Martin, C. Soudais, J. Bruneau, D. Boutboul, R. Rodriguez, C. Lenoir, A. D. Hislop, C. Besson, F. Touzot, et al. 2017. Inherited CD70 deficiency in humans reveals a critical role for the CD70-CD27 pathway in immunity to Epstein-Barr virus infection. J. Exp. Med. 214: 73-89.
31. Tesselaar, K., R. Arens, G. M. van Schijndel, P. A. Baars, M. A. van der Valk, J. Borst, M. H. van Oers, and R. A. van Lier. 2003. Lethal T cell immunodeficiency induced by chronic costimulation via CD27-CD70 interactions. Nat. Immunol. 4: 49-54.
32. Arens, R., K. Tesselaar, P. A. Baars, G. M. van Schijndel, J. Hendriks, S. T. Pals, P. Krimpenfort, J. Borst, M. H. van Oers, and R. A. van Lier. 2001. Constitutive CD27/CD70 interaction induces expansion of effector-type T cells and results in IFNgamma-mediated B cell depletion. Immunity 15: 801-812.
33. De Colvenaer, V., S. Taveirne, J. Hamann, A. M. de Bruin, M. De Smedt, T. Taghon, B. Vandekerckhove, J. Plum, R. van Lier, and G. Leclercq. 2010. Continuous CD27 triggering in vivo strongly reduces NK cell numbers. Eur. J. Immunol. 40: 1107-1117.
34. van Gisbergen, K. P., R. W. van Olffen, J. van Beek, K. F. van der Sluijs, R. Arens, M. A. Nolte, and R. A. van Lier. 2009. Protective CD8 T cell memory is impaired during chronic CD70-driven costimulation. J. Immunol. 182: 5352-5362.
35. Penaloza-MacMaster, P., A. Ur Rasheed, S. S. Iyer, H. Yagita, B. R. Blazar, and R. Ahmed. 2011. Opposing effects of CD70 costimulation during acute and chronic lymphocytic choriomeningitis virus infection of mice. J. Virol. 85: 6168-6174.
36. Matter, M., B. Odermatt, H. Yagita, J. M. Nuoffer, and A. F. Ochsenbein. 2006. Elimination of chronic viral infection by blocking CD27 signaling. J. Exp. Med. 203: 2145-2155.
37. Wensveen, F. M., P. P. Unger, N. A. Kragten, I. A. Derks, A. Ten Brinke, R. Arens, R. A. van Lier, E. Eldering, and K. P. van Gisbergen. 2012. CD70-driven costimulation induces survival or Fas-mediated apoptosis of T cells depending on antigenic load. J. Immunol. 188: 4256-4267.
38. Claus, C., C. Riether, C. Schürch, M. S. Matter, T. Hilmenyuk, and A. F. Ochsenbein. 2012. CD27 signaling increases the frequency of regulatory T cells and promotes tumor growth. Cancer Res. 72: 3664-3676.
39. Coquet, J. M., J. C. Ribot, N. Babała, S. Middendorp, G. van der Horst, Y. Xiao, J. F. Neves, D. Fonseca-Pereira, H. Jacobs, D. J. Pennington, et al. 2013. Epithelial and dendritic cells in the thymic medulla promote CD4+Foxp3+ regulatory T cell development via the CD27-CD70 pathway. J. Exp. Med. 210: 715-728.
40. Miller, J., G. Eisele, G. Tabatabai, S. Aulwurm, G. von Kurthy, L. Stitz, P. Roth, and M. Weller. 2010. Soluble CD70: a novel immunotherapeutic agent for experimental glioblastoma. J. Neurosurg. 113: 280-285.
41. Rowley, T. F., and A. Al-Shamkhani. 2004. Stimulation by soluble CD70 promotes strong primary and secondary CD8+ cytotoxic T cell responses in vivo. J. Immunol. 172: 6039-6046.
42. Roberts, D. J., N. A. Franklin, L. M. Kingeter, H. Yagita, A. L. Tutt, M. J. Glennie, and T. N. Bullock. 2010. Control of established melanoma by CD27 stimulation is associated with enhanced effector function and persistence, and reduced PD-1 expression of tumor infiltrating CD8(+) T cells. J. Immun-other. 33: 769-779.
43. Sakanishi, T., and H. Yagita. 2010. Anti-tumor effects of depleting and non-depleting anti-CD27 monoclonal antibodies in immune-competent mice. Bio-chem. Biophys. Res. Commun. 393: 829-835.
44. French, R. R., V. Y. Taraban, G. R. Crowther, T. F. Rowley, J. C. Gray, P. W. Johnson, A. L. Tutt, A. Al-Shamkhani, and M. J. Glennie. 2007. Eradication of lymphoma by CD8 T cells following anti-CD40 monoclonal antibody therapy is critically dependent on CD27 costimulation. Blood 109: 4810-4815.
45. Vitale, L. A., L. Z. He, L. J. Thomas, J. Widger, J. Weidlick, A. Crocker, T. O'Neill, J. Storey, M. J. Glennie, D. M. Grote, et al. 2012. Development of a human monoclonal antibody for potential therapy of CD27-expressing lym-phoma and leukemia. Clin. Cancer Res. 18: 3812-3821.
46. He, L. Z., N. Prostak, L. J. Thomas, L. Vitale, J. Weidlick, A. Crocker, C. D. Pilsmaker, S. M. Round, A. Tutt, M. J. Glennie, et al. 2013. Agonist anti-human CD27 monoclonal antibody induces T cell activation and tumor immunity in human CD27-transgenic mice. J. Immunol. 191: 4174-4183.
47. Burris, H. A., J. R. Infante, S. M. Ansell, J. J. Nemunaitis, G. R. Weiss, V. M. Villalobos, B. I. Sikic, M. H. Taylor, D. W. Northfelt, W. E. Carson, III., et al. 2017. Safety and activity of varlilumab, a novel and first-in-class agonist anti-CD27 antibody, in patients with advanced solid tumors. J. Clin. Oncol. 35: 2028-2036.
48. Li, F., and J. V. Ravetch. 2011. Inhibitory Fcg receptor engagement drives adjuvant and anti-tumor activities of agonistic CD40 antibodies. Science 333: 1030-1034.
49. White, A. L., H. T. Chan, A. Roghanian, R. R. French, C. I. Mockridge, A. L. Tutt, S. V. Dixon, D. Ajona, J. S. Verbeek, A. Al-Shamkhani, et al. 2011. Interaction with FcgRIIB is critical for the agonistic activity of anti-CD40 monoclonal antibody. J. Immunol. 187: 1754-1763.
50. Onizuka, S., I. Tawara, J. Shimizu, S. Sakaguchi, T. Fujita, and E. Nakayama. 1999. Tumor rejection by in vivo administration of anti-CD25 (interleukin-2 receptor alpha) monoclonal antibody. Cancer Res. 59: 3128-3133.
51. Vonderheide, R. H., and M. J. Glennie. 2013. Agonistic CD40 antibodies and cancer therapy. Clin. Cancer Res. 19: 1035-1043.
52. Joshi, N. S., W. Cui, A. Chandele, H. K. Lee, D. R. Urso, J. Hagman, L. Gapin, and S. M. Kaech. 2007. Inflammation directs memory precursor and short-lived effector CD8(+) T cell fates via the graded expression of T-bet transcription factor. Immunity 27: 281-295.
53. Wherry, E. J., and M. Kurachi. 2015. Molecular and cellular insights into T cell exhaustion. Nat. Rev. Immunol. 15: 486-499.
54. Piconese, S., B. Valzasina, and M. P. Colombo. 2008. OX40 triggering blocks suppression by regulatory T cells and facilitates tumor rejection. [Published erratum appears in 2008 J. Exp. Med. 205: 1505.] J. Exp. Med. 205: 825-839.
55. Sutmuller, R. P., L. M. van Duivenvoorde, A. van Elsas, T. N. Schumacher, M. E. Wildenberg, J. P. Allison, R. E. Toes, R. Offringa, and C. J. Melief. 2001. 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: 823-832.
56. Diegmann, J., K. Junker, I. F. Loncarevic, S. Michel, B. Schimmel, and F. von Eggeling. 2006. Immune escape for renal cell carcinoma: CD70 mediates apo-ptosis in lymphocytes. Neoplasia 8: 933-938.
57. Arens, R., P. A. Baars, M. Jak, K. Tesselaar, M. van der Valk, M. H. van Oers, and R. A. van Lier. 2005. Cutting edge: CD95 maintains effector T cell ho-meostasis in chronic immune activation. J. Immunol. 174: 5915-5920.
58. Py, B., C. Slomianny, P. Auberger, P. X. Petit, and S. Benichou. 2004. Siva-1 and an alternative splice form lacking the death domain, Siva-2, similarly induce apoptosis in T lymphocytes via a caspase-dependent mitochondrial pathway. J. Immunol. 172: 4008-4017.
59. Allam, A., M. Swiecki, W. Vermi, J. D. Ashwell, and M. Colonna. 2014. Dual function of CD70 in viral infection: modulator of early cytokine responses and activator of adaptive responses. J. Immunol. 193: 871-878.
60. Jak, M., R. Mous, E. B. Remmerswaal, R. Spijker, A. Jaspers, A. Yagüe, E. Eldering, R. A. Van Lier, and M. H. Van Oers. 2009. Enhanced formation and survival of CD4+ CD25hi Foxp3+ T-cells in chronic lymphocytic leukemia. Leuk. Lymphoma 50: 788-801.
61. 2 T cells. Blood 110: 2537-2544.
62. Duggleby, R. C., T. N. Shaw, L. B. Jarvis, G. Kaur, and J. S. Gaston. 2007. CD27 expression discriminates between regulatory and non-regulatory cells after expansion of human peripheral blood CD4+ CD25+ cells. Immunology 121: 129-139.
63. Koenen, H. J., E. Fasse, and I. Joosten. 2005. CD27/CFSE-based ex vivo selection of highly suppressive alloantigen-specific human regulatory T cells. J. Immunol. 174: 7573-7583.