Predictive value of CLDN18.2 + CD8 + T cells in peripheral blood and tumor tissue for immunotherapy response and survival in gastric and pancreatic cancers.

750 Background: CLDN18.2 has emerged as a therapeutic target in gastric cancer (GC) and pancreatic ductal adenocarcinoma (PDAC). Recent evidence indicates that CLDN18.2 can be acquired by CD8 + T cells via trogocytosis, leading to impaired cytotoxicity, metabolic dysfunction, and systemic immune senescence. This study aims to evaluate the prognostic and predictive value of CLDN18.2 + CD8 + T cells in peripheral blood and tumor tissues of patients with GC or PDAC receiving immunotherapy. Methods: This prospective observational study has enrolled 300 patients with advanced CLDN18.2-positive GC (n=190) or PDAC (n=110) scheduled to receive anti-PD-1-based immunotherapy in Tianjin Medical University Cancer Institute & Hospital. Peripheral blood and tumor biopsies will be collected at baseline and during treatment. CLDN18.2 + CD8 + T cells will be quantified using flow cytometry and multiplex immunohistochemistry. Primary endpoints include objective response rate (ORR). Secondary endpoints include overall survival (OS) and correlation between CLDN18.2 + CD8 + T cell frequency and functional markers. Results: CLDN18.2 + CD8 + T cell levels in tumor and blood were significantly positively correlated (r=0.78, p < 0.001). Non-responders receiving anti-PD-1-based immunotherapy had higher infiltration in both tumor (GC: 18.2% vs. 6.4%, p