Tigit-fc promotes antitumor immunity

Abstract

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 shownto 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- A nd NK cell-mediated tumor reactivity, sustained memory-induced immunity in tumor rechallengemodels, 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 cellmediated 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.