Distribution, phenotype, functional and clinical relevance of CD8CD103 tissue-resident memory T cells in human gastric cancer.

CD8CD103 tissue-resident memory T cells (TRMs) are involved in tumor immune response and linked to favorable clinical outcome in human cancer. However, the distribution, phenotype, functional properties and clinical relevance of these cells in gastric cancer (GC) remain elusive. Here, our data show that, in comparison to non-tumor tissues, the percentages of CD8CD103 TRMs in tumors are significantly decreased. Most tumor-infiltrating CD8CD103 TRMs are CD45RACCR7 effector-memory cells with higher PD-1 and 4-1BB expression than those from non-tumor tissues. Further, tumor-infiltrating CD8CD103 TRMs show impaired cytolytic capacity due to decreased granzyme B and perforin expression. Moreover, ex vivo PD-1 blockade could restore the cytolytic capacity of tumor-infiltrating CD8CD103 TRMs, and such anti-PD-1-mediated reinvigoration of CD8CD103 TRMs could be further enhanced by 4-1BB co-stimulation. Finally, lower levels of Tumor-infiltrating CD8CD103 TRMs are positively correlated with GC progression and poor patients' survival. Our data suggest that restoring CD8CD103 TRM function by combining PD-1 blockade and 4-1BB co-stimulation may be a promising strategy for treating GC.