The landscape of TIGIT target and clinical application in diseases

Abstract

Immune checkpoint blockade has dramatically altered the concept of cancer therapeutics over the past few years. Beyond the existing classical pathways, novel immune checkpoints, such as T-cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif (ITIM) structural domain (TIGIT), have also emerged in recent years and have promising therapeutic potential. Recent researches have provided ample evidence that TIGIT is extensively involved in various cancerous and noncancerous diseases such as chronic inflammation, autoimmune diseases, abnormal pregnancy status, and most recently coronavirus disease 2019. In contrast to the programmed cell death receptor 1 pathway which primarily affects T-cell function, targeting TIGIT pathway regulates multiple types of immunocytes but has fewer immune-related adverse events. Owing to its unique advantages and extensive involvement in diseases, extensive clinical trials blockade TIGIT or combine it with other targets are ongoing, and numerous phase II clinical trials have already seen promising results. In this review, we summarized the existing research on TIGIT in various diseases and discussed the perspective and challenges related to targeting this molecular for therapy, with an attempt to provide directions for subsequent studies.