Intratumoral TIGIT(+) CD8(+) T-cell infiltration determines poor prognosis and immune evasion in patients with muscle-invasive bladder cancer

BACKGROUND: T-cell immunoglobulin and ITIM domain (TIGIT) is identified as a novel checkpoint receptor that can facilitate immune escape via mediating T-cell exhaustion in tumors. However, the clinical significance and immune contexture correlation of intratumoral TIGIT(+) CD8(+) T-cells remain to be further explored in muscle-invasive bladder cancer (MIBC). METHODS: 259 patients with MIBC from two clinical centers (Zhongshan Hospital, n=141; Shanghai Cancer Center, n=118) were analyzed to evaluate the prognostic value and immune contexture association of TIGIT(+) CD8(+) T-cells through immunohistochemistry. Fresh tumor tissue samples from 26 patients with MIBC were examined to discover the phenotype of this CD8 subpopulation by flow cytometry. RESULTS: High infiltration of intratumoral TIGIT(+) CD8(+) T-cells predicted poor overall survival (OS) and recurrence-free survival (RFS) in MIBC. For patients with stage II MIBC with low infiltration of TIGIT(+) CD8(+) cells, adjuvant chemotherapy (ACT) could significantly prolong their OS and RFS. Intratumoral TIGIT(+) CD8(+) T-cell abundance was correlated with impaired CD8(+) T-cell cytotoxicity and exhibited production of immunosuppressive cytokine IL-10. Further analysis of tumor-infiltrating immune cell landscape revealed TIGIT(+) CD8(+) T-cells were associated with suppressive immune contexture, including Th2 cells, regulatory T-cells, mast cells and neutrophils. CONCLUSION: Intratumoral TIGIT(+) CD8(+) T-cell abundance could serve as an independent prognosticator for clinical outcome and a predictive biomarker for inferior ACT responsiveness. Intratumoral TIGIT(+) CD8(+) T-cell abundance correlated with dampened CD8(+) T-cell antitumor immunity and immunosuppressive contexture abundance, highlighting a tumor-promoting role of TIGIT(+) CD8(+) T-cells.