TIGIT, A Novel Therapeutic Target for Tumor Immunotherapy

ABSTRACT

Co-inhibitory and co-stimulatory receptors act in concert to regulate adaptive immune cell function, and the balance of these receptors is essential for the maintenance of immune homeostasis. Tumors constitute highly suppressive microenvironments in which elevated expression of co-inhibitory receptors on tumor-infiltrating lymphocytes (TILs) is often found. Functional blockade of the co-inhibitory receptors such as cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell death 1 (PD-1) have yielded encouraging outcomes in tumors, generating substantial interest in seeking for additional co-inhibitory molecules that may act as potential interfering targets. T-cell Ig and ITIM domain (TIGIT) is a newly identified co-inhibitory receptor expressed by regulatory T cells (Tregs), activated T cells, and natural killer (NK) cells. Several groups reported consistently that TIGIT expression was elevated on CD8⁺ TILs and Tregs in a variety of tumors. Moreover, TIGIT blockade has exhibited therapeutic benefits in animal models of different tumors. Therefore, TIGIT upregulation plays an important role in tumor immunity and may serve as a promising therapeutic target for tumor management.

KEYWORDS:

• Co-inhibitory receptor
• TIGIT
• tumor immunity

Conflict of Interest and Financial Disclosures

The authors declare no competing financial interests.

Funding

This work was supported by grants from National Natural Science Foundation of China (No. 81200344, No.81570103).