Targeting TIGIT for cancer immunotherapy: recent advances and future directions

Peng Zhang; Xinyuan Liu; Zhuoyu Gu; Zhongxing Jiang; Song Zhao; Yongping Song; Jifeng Yu

doi:10.1186/s40364-023-00543-z

Targeting TIGIT for cancer immunotherapy: recent advances and future directions

Biomark Res. 2024 Jan 16;12(1):7. doi: 10.1186/s40364-023-00543-z.

Authors

Peng Zhang^#^{1

2}, Xinyuan Liu^#³, Zhuoyu Gu^#^{1

2}, Zhongxing Jiang⁴, Song Zhao⁵, Yongping Song⁶, Jifeng Yu^{7

8}

Affiliations

¹ Department of Thoracic Surgery, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China.
² Henan Medical Key Laboratory of Thoracic Oncology, Zhengzhou, 450052, Henan, China.
³ Institute of Biomedical Informatics, Bioinformatics Center, Henan Provincial Engineering Center for Tumor Molecular Medicine, School of Basic Medical Sciences, Henan University, Kaifeng, 475004, Henan, China.
⁴ Department of Hematology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China.
⁵ Department of Thoracic Surgery, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China. zhaosong@zzu.edu.cn.
⁶ Department of Hematology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China. Songyongping001@126.com.
⁷ Department of Hematology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China. Yujifengzzu@163.com.
⁸ Henan International Joint Laboratory of Nuclear Protein Gene Regulation, Henan University College of Medicine, Kaifeng, 475004, Henan, China. Yujifengzzu@163.com.

^# Contributed equally.

Abstract

As a newly identified checkpoint, T cell immunoreceptor with immunoglobulin and tyrosine-based inhibitory motif (ITIM) domain (TIGIT) is highly expressed on CD4⁺ T cells, CD8⁺ T cells, natural killer (NK) cells, regulatory T cells (Tregs), and tumor-infiltrating lymphocytes (TILs). TIGIT has been associated with NK cell exhaustion in vivo and in individuals with various cancers. It not only modulates NK cell survival but also mediates T cell exhaustion. As the primary ligand of TIGIT in humans, CD155 may be the main target for immunotherapy due to its interaction with TIGIT. It has been found that the anti-programmed cell death protein 1 (PD-1) treatment response in cancer immunotherapy is correlated with CD155 but not TIGIT. Anti-TIGIT alone and in combination with anti-PD-1 agents have been tested for cancer immunotherapy. Although two clinical studies on advanced lung cancer had positive results, the TIGIT-targeted antibody, tiragolumab, recently failed in two new trials. In this review, we highlight the current developments on TIGIT for cancer immunotherapy and discuss the characteristics and functions of TIGIT.

Keywords: Clinical trial; Immune checkpoint pathway; TIGIT; Target immunotherapy; cancer immunotherapy.

Publication types

Review