TIGIT-Fc Promotes Antitumor Immunity

• Published in: Cancer immunology research 2021-09, Vol.9 (9), p.1088-1097
• Main Authors: Shen, Xian, Fu, Wenyan, Wei, Yongpeng, Zhu, Junle, Yu, Yue, Lei, Changhai, Zhao, Jian, Hu, Shi
• Format: Article
• Language: English
• Subjects: Animals; B7-H1 Antigen - genetics; B7-H1 Antigen - metabolism; Cell Line, Tumor; Female; Humans; Immune Tolerance; Killer Cells, Natural - immunology; Mice; Mice, Inbred BALB C; Mice, Inbred NOD; Mice, Nude; Mice, SCID; Neoplasms, Experimental - immunology; Neoplasms, Experimental - metabolism; Receptors, Immunologic - antagonists & inhibitors; Receptors, Immunologic - genetics; Receptors, Immunologic - metabolism; T-Lymphocytes - immunology; Xenograft Model Antitumor Assays
• ISSN: 2326-6066; 2326-6074
• DOI: 10.1158/2326-6066.CIR-20-0986

T-cell immunoreceptor with Ig and ITIM domains (TIGIT) is a checkpoint receptor that mediates both T-cell and natural killer (NK)-cell exhaustion in tumors. An Fc-TIGIT fusion protein was shown to induce an immune-tolerance effect in a previous report, but the relevance of the TIGIT-Fc protein to tumor immunity is unknown. Here, we found that TIGIT-Fc promotes, rather than suppresses, tumor immunity. TIGIT-Fc treatment promoted the effector function of CD8 T and NK cells in several tumor-bearing mouse models. TIGIT-Fc treatment resulted in potent T cell- and NK cell-mediated tumor reactivity, sustained memory-induced immunity in tumor rechallenge models, enhanced therapeutic effects via an antibody against PD-L1, and induction of Th1 development in CD4 T cells. TIGIT-Fc showed a potent antibody-dependent cell-mediated cytotoxicity effect but had no intrinsic effect on tumor cell development. Our findings elucidate the role of TIGIT-Fc in tumor immune reprogramming, suggesting that TIGIT-Fc treatment alone or in combination with other checkpoint receptor blockers is a promising anticancer therapeutic strategy.