Deficiency of host CD96 and PD-1 or TIGIT enhances tumor immunity without significantly compromising immune homeostasis

References

• Smyth MJ, Ngiow SF, Ribas A, Teng MW. Combination cancer immunotherapies tailored to the tumour microenvironment. Nat Rev Clin Oncol. 2016;13:143–58. doi:10.1038/nrclinonc.2015.209. PMID:26598942.
   PubMed Web of Science ®Google Scholar
• Larkin J, Chiarion-Sileni V, Gonzalez R, Grob JJ, Cowey CL, Lao CD, Schadendorf D, Dummer R, Smylie M, Rutkowski P, et al. Combined Nivolumab and Ipilimumab or Monotherapy in Untreated Melanoma. N Engl J Med. 2015;373:23–34. doi:10.1056/NEJMoa1504030. PMID:26027431.
   PubMed Web of Science ®Google Scholar
• Boutros C, Tarhini A, Routier E, Lambotte O, Ladurie FL, Carbonnel F, Izzeddine H, Marabelle A, Champiat S, Berdelou A, et al. Safety profiles of anti-CTLA-4 and anti-PD-1 antibodies alone and in combination. Nat Rev Clin Oncol. 2016;13:473–86. doi:10.1038/nrclinonc.2016.58. PMID:27141885.
   PubMed Web of Science ®Google Scholar
• Pardoll DM. The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer. 2012;12:252–64. doi:10.1038/nrc3239. PMID:22437870.
   PubMed Web of Science ®Google Scholar
• Tivol EA, Borriello F, Schweitzer AN, Lynch WP, Bluestone JA, Sharpe AH. Loss of CTLA-4 leads to massive lymphoproliferation and fatal multiorgan tissue destruction, revealing a critical negative regulatory role of CTLA-4. Immunity. 1995;3:541–7. doi:10.1016/1074-7613(95)90125-6. PMID:7584144.
   PubMed Web of Science ®Google Scholar
• Waterhouse P, Penninger JM, Timms E, Wakeham A, Shahinian A, Lee KP, Thompson CB, Griesser H, Mak TW. Lymphoproliferative disorders with early lethality in mice deficient in Ctla-4. Science. 1995;270:985–8. doi:10.1126/science.270.5238.985. PMID:7481803.
   PubMed Web of Science ®Google Scholar
• Nishimura H, Nose M, Hiai H, Minato N, Honjo T. Development of lupus-like autoimmune diseases by disruption of the PD-1 gene encoding an ITIM motif-carrying immunoreceptor. Immunity. 1999;11:141–51. doi:10.1016/S1074-7613(00)80089-8. PMID:10485649.
   PubMed Web of Science ®Google Scholar
• Nishimura H, Okazaki T, Tanaka Y, Nakatani K, Hara M, Matsumori A, Sasayama S, Mizoguchi A, Hiai H, Minato N, et al. Autoimmune dilated cardiomyopathy in PD-1 receptor-deficient mice. Science. 2001;291:319–22. doi:10.1126/science.291.5502.319. PMID:11209085.
   PubMed Web of Science ®Google Scholar
• Latchman YE, Liang SC, Wu Y, Chernova T, Sobel RA, Klemm M, Kuchroo VK, Freeman GJ, Sharpe AH. PD-L1-deficient mice show that PD-L1 on T cells, antigen-presenting cells, and host tissues negatively regulates T cells. Proc Natl Acad Sci U S A. 2004;101:10691–6. doi:10.1073/pnas.0307252101. PMID:15249675.
   PubMed Web of Science ®Google Scholar
• Dong H, Zhu G, Tamada K, Flies DB, van Deursen JM, Chen L. B7-H1 determines accumulation and deletion of intrahepatic CD8(+) T lymphocytes. Immunity. 2004;20:327–36. doi:10.1016/S1074-7613(04)00050-0. PMID:15030776.
   PubMed Web of Science ®Google Scholar
• Woo SR, Turnis ME, Goldberg MV, Bankoti J, Selby M, Nirschl CJ, Bettini ML, Gravano DM, Vogel P, Liu CL, et al. Immune inhibitory molecules LAG-3 and PD-1 synergistically regulate T-cell function to promote tumoral immune escape. Cancer Res. 2012;72:917–27. doi:10.1158/0008-5472.CAN-11-1620. PMID:22186141.
   PubMed Web of Science ®Google Scholar
• Zhu G, Augustine MM, Azuma T, Luo L, Yao S, Anand S, Rietz AC, Huang J, Xu H, Flies AS, et al. B7-H4-deficient mice display augmented neutrophil-mediated innate immunity. Blood. 2009;113:1759–67. doi:10.1182/blood-2008-01-133223. PMID:19109567.
   PubMed Web of Science ®Google Scholar
• Liu J, Yuan Y, Chen W, Putra J, Suriawinata AA, Schenk AD, Miller HE, Guleria I, Barth RJ, Huang YH, et al. Immune-checkpoint proteins VISTA and PD-1 nonredundantly regulate murine T-cell responses. Proc Natl Acad Sci U S A. 2015;112:6682–7. doi:10.1073/pnas.1420370112. PMID:25964334.
   Web of Science ®Google Scholar
• Martinet L, Smyth MJ. Balancing natural killer cell activation through paired receptors. Nat Rev Immunol. 2015;15:243–54. doi:10.1038/nri3799. PMID:25743219.
   PubMed Web of Science ®Google Scholar
• Blake SJ, Dougall WC, Miles JJ, Teng MW, Smyth MJ. Molecular Pathways: Targeting CD96 and TIGIT for Cancer Immunotherapy. Clin Cancer Res. 2016;22:5183–8. doi:10.1158/1078-0432.CCR-16-0933. PMID:27620276.
   PubMed Web of Science ®Google Scholar
• Wang PL, O'Farrell S, Clayberger C, Krensky AM. Identification and molecular cloning of tactile. A novel human T cell activation antigen that is a member of the Ig gene superfamily. J Immunol. 1992;148:2600–8. PMID:1313846.
   PubMed Web of Science ®Google Scholar
• Seth S, Maier MK, Qiu Q, Ravens I, Kremmer E, Forster R, Bernhardt G. The murine pan T cell marker CD96 is an adhesion receptor for CD155 and nectin-1. Biochem Biophys Res Commun. 2007;364:959–65. doi:10.1016/j.bbrc.2007.10.102. PMID:17971293.
   PubMed Web of Science ®Google Scholar
• Yu X, Harden K, Gonzalez LC, Francesco M, Chiang E, Irving B, Tom I, Ivelja S, Refino CJ, Clark H, et al. The surface protein TIGIT suppresses T cell activation by promoting the generation of mature immunoregulatory dendritic cells. Nat Immunol. 2009;10:48–57. doi:10.1038/ni.1674. PMID:19011627.
   PubMed Web of Science ®Google Scholar
• Levin SD, Taft DW, Brandt CS, Bucher C, Howard ED, Chadwick EM, Johnston J, Hammond A, Bontadelli K, Ardourel D, et al. Vstm3 is a member of the CD28 family and an important modulator of T-cell function. Eur J Immunol. 2011;41:902–15. doi:10.1002/eji.201041136. PMID:21416464.
   PubMed Web of Science ®Google Scholar
• Fuchs A, Cella M, Giurisato E, Shaw AS, Colonna M. Cutting edge: CD96 (tactile) promotes NK cell-target cell adhesion by interacting with the poliovirus receptor (CD155). J Immunol. 2004;172:3994–8. doi:10.4049/jimmunol.172.7.3994. PMID:15034010.
   PubMed Web of Science ®Google Scholar
• Shibuya A, Campbell D, Hannum C, Yssel H, Franz-Bacon K, McClanahan T, Kitamura T, Nicholl J, Sutherland GR, Lanier LL, et al. DNAM-1, a novel adhesion molecule involved in the cytolytic function of T lymphocytes. Immunity. 1996;4:573–81. doi:10.1016/S1074-7613(00)70060-4. PMID:8673704.
   PubMed Web of Science ®Google Scholar
• Bottino C, Castriconi R, Pende D, Rivera P, Nanni M, Carnemolla B, Cantoni C, Grassi J, Marcenaro S, Reymond N, et al. Identification of PVR (CD155) and Nectin-2 (CD112) as cell surface ligands for the human DNAM-1 (CD226) activating molecule. J Exp Med. 2003;198:557–67. doi:10.1084/jem.20030788. PMID:12913096.
   PubMed Web of Science ®Google Scholar
• Zhu Y, Paniccia A, Schulick AC, Chen W, Koenig MR, Byers JT, Yao S, Bevers S, Edil BH. Identification of CD112R as a novel checkpoint for human T cells. J Exp Med. 2016;213:167–76. doi:10.1084/jem.20150785. PMID:26755705.
   PubMed Web of Science ®Google Scholar
• Chan CJ, Martinet L, Gilfillan S, Souza-Fonseca-Guimaraes F, Chow MT, Town L, Ritchie DS, Colonna M, Andrews DM, Smyth MJ. The receptors CD96 and CD226 oppose each other in the regulation of natural killer cell functions. Nat Immunol. 2014;15:431–8. doi:10.1038/ni.2850. PMID:24658051.
   PubMed Web of Science ®Google Scholar
• Blake SJ, Stannard K, Liu J, Allen S, Yong MC, Mittal D, Aguilera AR, Miles JJ, Lutzky VP, de Andrade LF, et al. Suppression of metastases using a new lymphocyte checkpoint target for cancer immunotherapy. Cancer Discov. 2016;6:446/59. doi:10.1158/2159-8290.CD-15-0944. PMID:26787820.
   Web of Science ®Google Scholar
• Chauvin JM, Pagliano O, Fourcade J, Sun Z, Wang H, Sander C, Kirkwood JM, Chen TH, Maurer M, Korman AJ, et al. TIGIT and PD-1 impair tumor antigen-specific CD8(+) T cells in melanoma patients. J Clin Invest. 2015;125:2046–58. doi:10.1172/JCI80445. PMID:25866972.
   PubMed Web of Science ®Google Scholar
• Johnston Robert J, Comps-Agrar L, Hackney J, Yu X, Huseni M, Yang Y, Park S, Javinal V, Chiu H, Irving B, et al. The Immunoreceptor TIGIT Regulates Antitumor and Antiviral CD8+ T Cell Effector Function. Cancer Cell. 2014;26:923–37. doi:10.1016/j.ccell.2014.10.018. PMID:25465800.
   PubMed Web of Science ®Google Scholar
• Lozano E, Dominguez-Villar M, Kuchroo V, Hafler DA. The TIGIT/CD226 axis regulates human T cell function. J Immunol. 2012;188:3869–75. doi:10.4049/jimmunol.1103627. PMID:22427644.
   PubMed Web of Science ®Google Scholar
• Kurtulus S, Sakuishi K, Ngiow SF, Joller N, Tan DJ, Teng MW, Smyth MJ, Kuchroo VK, Anderson AC. TIGIT predominantly regulates the immune response via regulatory T cells. J Clin Invest. 2015;125:4053–62. doi:10.1172/JCI81187. PMID:26413872.
   PubMed Web of Science ®Google Scholar
• Joller N, Lozano E, Burkett Patrick R, Patel B, Xiao S, Zhu C, Xia J, Tan TG, Sefik E, Yajnik V, et al. Treg Cells Expressing the Coinhibitory Molecule TIGIT Selectively Inhibit Proinflammatory Th1 and Th17 Cell Responses. Immunity. 2014;40:569–81. doi:10.1016/j.immuni.2014.02.012. PMID:24745333.
   PubMed Web of Science ®Google Scholar
• Ellestad KK, Thangavelu G, Ewen CL, Boon L, Anderson CC. PD-1 is not required for natural or peripherally induced regulatory T cells: Severe autoimmunity despite normal production of regulatory T cells. Eur J Immunol. 2014;44:3560–72. doi:10.1002/eji.201444688. PMID:25236923.
   PubMed Web of Science ®Google Scholar
• Chen X, Fosco D, Kline DE, Meng L, Nishi S, Savage PA, Kline J. PD-1 regulates extrathymic regulatory T-cell differentiation. Eur J Immunol. 2014;44:2603–16. doi:10.1002/eji.201344423. PMID:24975127.
   PubMed Web of Science ®Google Scholar
• Ngiow SF, Young A, Jacquelot N, Yamazaki T, Enot D, Zitvogel L, Smyth MJ. A Threshold Level of Intratumor CD8+ T-cell PD1 Expression Dictates Therapeutic Response to Anti-PD1. Cancer Research. 2015;75:3800–11. doi:10.1158/0008-5472.CAN-15-1082. PMID:26208901.
   PubMed Web of Science ®Google Scholar
• Knight DA, Ngiow SF, Li M, Parmenter T, Mok S, Cass A, Haynes NM, Kinross K, Yagita H, Koya RC, et al. Host immunity contributes to the anti-melanoma activity of BRAF inhibitors. J Clin Invest. 2013;123:1371–81. doi:10.1172/JCI66236. PMID:23454771.
   PubMed Web of Science ®Google Scholar
• Haynes NM, Hawkins ED, Li M, McLaughlin NM, Hammerling GJ, Schwendener R, Winoto A, Wensky A, Yagita H, Takeda K, et al. CD11 c+ dendritic cells and B cells contribute to the tumoricidal activity of anti-DR5 antibody therapy in established tumors. J Immunol. 2010;185:532–41. doi:10.4049/jimmunol.0903624. PMID:20505139.
   PubMed Web of Science ®Google Scholar
• Gao Y, Souza-Fonseca-Guimaraes F, Bald T, Ng SS, Young A, Ngiow SF, Rautela J, Straube J, Waddell N, Blake SJ, et al. Tumor immunoevasion by the conversion of effector NK cells into type 1 innate lymphoid cells. Nat Immunol. 2017;18:1004–15. PMID:28759001.
   PubMed Web of Science ®Google Scholar
• Young A, Ngiow SF, Gao Y, Patch AM, Barkauskas DS, Messaoudene M, Lin G, Coudert JD, Stannard KA, Zitvogel L, et al. A2AR adenosine signaling suppresses natural killer cell maturation in the tumor microenvironment. Cancer Res. 2018;78:1003–16. doi:10.1158/0008-5472.can-17-2826. PMID:29229601.
   PubMed Web of Science ®Google Scholar
• Bettini M, Szymczak-Workman AL, Forbes K, Castellaw AH, Selby M, Pan X, Drake CG, Korman AJ, Vignali DA. Cutting edge: accelerated autoimmune diabetes in the absence of LAG-3. J Immunol. 2011;187:3493–8. doi:10.4049/jimmunol.1100714. PMID:21873518.
   PubMed Web of Science ®Google Scholar
• Okazaki T, Okazaki IM, Wang J, Sugiura D, Nakaki F, Yoshida T, Kato Y, Fagarasan S, Muramatsu M, Eto T, et al. PD-1 and LAG-3 inhibitory co-receptors act synergistically to prevent autoimmunity in mice. J Exp Med. 2011;208:395–407. doi:10.1084/jem.20100466. PMID:21300912.
   PubMed Web of Science ®Google Scholar
• Wang J, Yoshida T, Nakaki F, Hiai H, Okazaki T, Honjo T. Establishment of NOD-Pdcd1-/- mice as an efficient animal model of type I diabetes. Proc Natl Acad Sci U S A. 2005;102:11823–8. doi:10.1073/pnas.0505497102. PMID:16087865.
   PubMed Web of Science ®Google Scholar
• Hughes J, Vudattu N, Sznol M, Gettinger S, Kluger H, Lupsa B, Herold KC. Precipitation of autoimmune diabetes with anti-PD-1 immunotherapy. Diabetes Care. 2015;38:e55–7. PMID:25805871.
   PubMed Web of Science ®Google Scholar
• Byun DJ, Wolchok JD, Rosenberg LM, Girotra M. Cancer immunotherapy – immune checkpoint blockade and associated endocrinopathies. Nat Rev Endocrinol. 2017;13:195–207. doi:10.1038/nrendo.2016.205. PMID:28106152.
   PubMed Web of Science ®Google Scholar
• Juneja VR, McGuire KA, Manguso RT, LaFleur MW, Collins N, Haining WN, Freeman GJ, Sharpe AH. PD-L1 on tumor cells is sufficient for immune evasion in immunogenic tumors and inhibits CD8 T cell cytotoxicity. J Exp Med. 2017;214:895–904. doi:10.1084/jem.20160801. PMID:28302645.
   PubMed Web of Science ®Google Scholar
• Nishimura H, Minato N, Nakano T, Honjo T. Immunological studies on PD-1 deficient mice: implication of PD-1 as a negative regulator for B cell responses. Int Immunol. 1998;10:1563–72. doi:10.1093/intimm/10.10.1563. PMID:9796923.
   PubMed Web of Science ®Google Scholar
• Stagg J, Divisekera U, Duret H, Sparwasser T, Teng MW, Darcy PK, Smyth MJ. CD73-deficient mice have increased antitumor immunity and are resistant to experimental metastasis. Cancer Res. 2011;71:2892–900. doi:10.1158/0008-5472.CAN-10-4246. PMID:21292811.
   PubMed Web of Science ®Google Scholar
• Ferrari de Andrade L, Ngiow SF, Stannard K, Rusakiewicz S, Kalimutho M, Khanna KK, Tey SK, Takeda K, Zitvogel L, Martinet L, et al. Natural killer cells are essential for the ability of BRAF inhibitors to control BRAFV600E-mutant metastatic melanoma. Cancer Res. 2014;74:7298–308. doi:10.1158/0008-5472.CAN-14-1339. PMID:25351955.
   PubMed Web of Science ®Google Scholar
• Groom JR, Fletcher CA, Walters SN, Grey ST, Watt SV, Sweet MJ, Smyth MJ, Mackay CR, Mackay F. BAFF and MyD88 signals promote a lupuslike disease independent of T cells. J Exp Med. 2007;204:1959–71. doi:10.1084/jem.20062567. PMID:17664289.
   PubMed Web of Science ®Google Scholar
• Mayer CT, Tian L, Hesse C, Kuhl AA, Swallow M, Kruse F, Thiele M, Gershwin ME, Liston A, Sparwasser T. Anti-CD4 treatment inhibits autoimmunity in scurfy mice through the attenuation of co-stimulatory signals. J Autoimmun. 2014;50:23–32. doi:10.1016/j.jaut.2013.08.010. PMID:24075450.
   PubMed Web of Science ®Google Scholar
• Teng MW, Ngiow SF, von Scheidt B, McLaughlin N, Sparwasser T, Smyth MJ. Conditional regulatory T-cell depletion releases adaptive immunity preventing carcinogenesis and suppressing established tumor growth. Cancer Res. 2010;70:7800–9. doi:10.1158/0008-5472.CAN-10-1681. PMID:20924111.
   PubMed Web of Science ®Google Scholar