Journal
CANCER IMMUNOLOGY RESEARCH
Volume 9, Issue 9, Pages 1088-1097Publisher
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/2326-6066.CIR-20-0986
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Funding
- National Natural Science Foundation of China [81773261, 31970882, 81903140, 81670573, 81972252, 81602690]
- Shanghai Rising-Star Program [19QA1411400]
- Shanghai Sailing Program [19YF1438600]
- Shanghai Chenguang Program [17CG35]
- Shanghai Biomedical Technology Support Project [20S11906600]
- Engineering Research Center of Cell & Therapeutic Antibody, Ministry of Education, of Shanghai Jiao Tong University
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TIGIT-Fc protein promotes tumor immunity by enhancing effector functions of CD8(+) T and NK cells, inducing Th1 development in CD4(+) T cells, and providing potent antibody-dependent cell-mediated cytotoxicity effects, suggesting it as a promising anticancer therapeutic strategy either alone or in combination with other checkpoint receptor blockers.
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.
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