Malignant tumors remain a major threat to human health, and conventional treatments and first-generation immune checkpoint inhibitors (ICIs) face limitations such as drug resistance and low response rates. The comprehensive review is now available online on September 22, 2025 and was published in the journal Volume 9, Issue 1. Pancreatology Journal March 30, 2026 T-cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domains (TIGITs) are highlighted as promising second-generation targets to address these challenges.
Unlike LAG-3, TIM-3, and other emerging checkpoints, TIGIT is widely expressed on T cells, natural killer (NK) cells, and regulatory T cells (Tregs), and primarily binds competitively to CD155/CD112 ligands to block CD226 signaling and inhibits T and NK It exerts its immunosuppressive effects through multiple pathways by inhibiting cellular function and promoting a hypoxic, immunosuppressive tumor microenvironment. (time).
Clinical evidence associates elevated TIGIT expression with poor prognosis in multiple cancers, including breast, colorectal, and pancreatic cancers. For example, TCGA data show that higher TIGIT levels in breast cancer tissue correlate with shorter overall survival and progression-free time. Notably, TIGIT outperforms PD-1 in defining tumor CD8+ T cell phenotypes, highlighting its potential as a prognostic and therapeutic marker.
Although TIGIT monotherapy is not very effective, its combination with PD-1 inhibitors has shown significant promise. Clinical trials such as the phase II CITYSCAPE trial have demonstrated that combination therapy of tiragolumab (anti-TIGIT) and atezolizumab (anti-PD-1) significantly improves objective remission rates and progression-free survival compared to PD-1 monotherapy, with a manageable safety profile. This synergistic effect arises from TIGIT’s ability to reverse T cell depletion, prevent NK cell depletion, and address PD-1 resistance.
Current TIGIT inhibitors such as vivostrimab, tiragolumab, and ocipelimab are in phase III trials, and dual-targeted agents such as candonilimab (TIGIT/CTLA-4) are also in development. Future studies will focus on biomarker validation, dose optimization, and combining TIGIT inhibition with metabolic or epigenetic interventions to increase efficacy.
”TIGIT-centric immunotherapy provides a translational framework to overcome tumor diversity and immunotherapy resistance” note the review authors, highlighting its potential to revolutionize the treatment of solid tumors and hematologic malignancies.
sauce:
Chinese Medical Journal Publishing Co., Ltd.
Reference magazines:
Lee, H. Others. (2026). Role of TIGIT in tumor progression and immune evasion. Pancreatology Journal. DOI: 10.1097/JP9.0000000000000245. https://journals.lww.com/jpancreatology/fulltext/2026/03000/role_of_tigit_in_tumor_progression_and_immune.2.aspx
