TIGIT-Fc Promotes Antitumor Immunity

  • Cancer Immunol Res. 2021 Sep;9(9):1088-1097. doi: 10.1158/2326-6066.CIR-20-0986.
Xian Shen  #  1 ,  Wenyan Fu  #  2  3 ,  Yongpeng Wei  #  4 ,  Junle Zhu  2  5 ,  Yue Yu  2  6 ,  Changhai Lei  2 ,  Jian Zhao  7  8 ,  Shi Hu  9
Affiliations
  • 1. Department of Gastrointestinal Surgery, The Second Affiliated Hospital, Wenzhou Medical University, Wenzhou, P.R. China.
  • 2. Department of Biophysics, College of Basic Medical Sciences, Second Military Medical University, Shanghai, P.R. China.
  • 3. Department of Assisted Reproduction, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, P.R. China.
  • 4. The Fifth Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, P.R. China.
  • 5. Department of Neurosurgery, Tongji Hospital, Tongji University School of Medicine, Shanghai, P.R. China.
  • 6. Department of Thyroid and Breast Surgery, First Affiliated Hospital, Second Military Medical University, Shanghai, P.R. China.
  • 7. Shanghai Key Laboratory of Molecular Imaging, Shanghai University of Medicine and Health Sciences, Shanghai, P.R. China.
  • 8. KOCHKOR Biotech, Inc., Shanghai, P.R. China.
  • 9. Department of Biophysics, College of Basic Medical Sciences, Second Military Medical University, Shanghai, P.R. China. [email protected].
  • # Contributed equally.
PMID: 34244300 DOI: 10.1158/2326-6066.CIR-20-0986
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 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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