Qilu Hospital of Shandong University

TIGIT Emerges as a Breakthrough Second-Generation Immune Checkpoint Target to Overcome Cancer Immunotherapy Resistance

- TIGIT is broadly expressed on T cells, NK cells, and regulatory T cells, exerting immunosuppressive effects by competitively binding CD155 and CD112 ligands to block CD226 co-stimulatory signaling. - Elevated TIGIT expression correlates with poor prognosis across multiple cancers including breast, colorectal, and pancreatic malignancies, and outperforms PD-1 in defining exhausted CD8+ T-cell phenotypes. - The phase II CITYSCAPE trial demonstrated that combining anti-TIGIT antibody tiragolumab with anti-PD-1 agent atezolizumab significantly improved objective response rates and progression-free survival in NSCLC patients. - Several TIGIT inhibitors including vibostolimab, tiragolumab, and ociperlimab are advancing through phase III trials, with dual-target agents like candonilimab (TIGIT/CTLA-4) also under development.