TIGIT-Fc Promotes Antitumor Immunity
| Autor: | Xian Shen, Shi Hu, Changhai Lei, Yongpeng Wei, Yue Yu, Junle Zhu, Wenyan Fu, Jian Zhao |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Cancer Research
T-Lymphocytes T cell Immunology Mice Nude Mice SCID B7-H1 Antigen Mice Immune system TIGIT Mice Inbred NOD Immunity Cell Line Tumor Immune Tolerance medicine Animals Humans Receptors Immunologic Receptor Mice Inbred BALB C biology Chemistry Neoplasms Experimental Xenograft Model Antitumor Assays Fusion protein Killer Cells Natural medicine.anatomical_structure Cancer research biology.protein Female Antibody CD8 |
| Zdroj: | Cancer Immunology Research. 9:1088-1097 |
| ISSN: | 2326-6074 2326-6066 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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