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bioRxiv · 10.1101/2020.10.19.346437

TIGIT-Fc Promotes Antitumour Immunity

Fu, W.·Lei, C.·Zhao, J.·Hu, S.
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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 tumours. 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 tumour immunity is unknown. Here, we unexpectedly found that TIGIT-Fc promotes rather than suppresses tumour immunity. TIGIT-Fc treatment promoted the effector function of CD8+ T and NK cells in several tumour-bearing mouse models. Additionally, TIGIT-Fc treatment resulted in potent T cell and NK-cell-mediated tumour reactivity, sustained memory-induced immunity in tumour re-challenge 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 (ADCC) effect but no intrinsic effect on tumour cell development. Our findings elucidate the unexpected role of TIGIT-Fc in tumour 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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Fu, W., Lei, C., Zhao, J., Hu, S.. 2020-10-21. TIGIT-Fc Promotes Antitumour Immunity. https://doi.org/10.1101/2020.10.19.346437

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