TIGIT⁺ CD4⁺ T Cell Enrichment in Colorectal Liver Metastases Is Associated with Shorter Survival

The immune microenvironment of colorectal cancer liver metastases (CRCLM) differs from that of primary colorectal tumors and may influence responses to immunotherapy. We aimed to characterize T cell subsets and checkpoint receptor expression in CRCLM and explore associations with overall survival.

We performed flow cytometric profiling of matched peripheral blood, non-tumor liver tissue, and CRCLM specimens from 17 patients undergoing hepatic metastasectomy. A separate cohort of 19 patients was studied using ex vivo expanded TILs. Kaplan-Meier/log-rank analyses were complemented by Cox models using dichotomized and continuous marker values, median-cut-off and permutation sensitivity analyses, and post hoc clinical covariate comparisons.

CRCLM showed relative enrichment of CD4⁺ T cells and depletion of CD8⁺ T cells. In the fresh cohort, 16 patients (12 deaths) were evaluable for CRCLM TIGIT⁺ CD4⁺ cells. The optimized split was associated with shorter survival for the high group (HR 5.26, 95% CI 1.54-17.94; log-rank p = 0.0036). The median-cut-off analysis showed the same direction (HR 3.17, 95% CI 0.92-11.00; p = 0.0551), as did the continuous model (HR 1.69 per 10-percentage-point increase, 95% CI 0.82-3.45; p = 0.153). In the expanded cohort, the optimized high-versus-low HR was 17.47 (95% CI 3.23-94.59; p < 0.001), and the continuous HR was directionally concordant (HR 2.68, 95% CI 0.96-7.51; p = 0.060). Clinical characteristics were balanced between optimized low and high groups.

TIGIT⁺ CD4⁺ T cell enrichment showed an exploratory association with shorter survival in CRCLM and represents a promising candidate for further prognostic and functional investigation. The separate expanded cohort provided complementary evidence supporting this observation.