Neoadjuvant chemotherapy plus PD-1 blockade for locally advanced gastric cancer: Clinical outcomes and CD103+CD8+ T cells as a response-associated biomarker

Introduction Programmed death-1 (PD-1) inhibitors combined with chemotherapy are established for advanced gastric cancer, but their role in the neoadjuvant treatment of locally advanced gastric cancer (LAGC) remains incompletely defined. Biomarkers associated with pathological response are also needed to improve patient stratification. Methods This retrospective cohort included 144 patients with LAGC who received neoadjuvant chemotherapy plus a PD-1 inhibitor followed by curative-intent surgery between June 2021 and December 2025. Pathological and radiographic responses, survival, surgical outcomes, and treatment-related adverse events were evaluated. Multiplex immunofluorescence was performed in paired tumor specimens from an exploratory subset of 36 sintilimab-treated patients. Multivariable logistic and Cox regression analyses were used to assess factors associated with pathological response and survival. Results The pathological complete response (pCR) and major pathological response (MPR) rates were 18.0% and 36.0%, respectively, and the R0 resection rate was 95.0%. The 1-year overall survival (OS) and disease-free survival (DFS) rates were 86.9% and 77.4%, respectively. Grade 1–2 treatment-related adverse events occurred in 91.7% of patients and grade 3 events in 30.6%; no grade 4 or 5 events occurred. PD-L1 CPS ≥1 was independently associated with a higher likelihood of MPR (adjusted OR for non-MPR, 0.31; 95% CI, 0.13–0.70; P = 0.006), but was not independently associated with OS or DFS. Baseline intratumoral CD103 + CD8 + T-cell density was numerically higher in responders than in non-responders, but this difference was not significant after false discovery rate correction (adjusted P = 0.0662). Paired analyses showed a greater treatment-associated increase in CD103 + CD8 + T-cell density among responders, whereas no statistically significant difference in CD103 - CD8 + T-cell density was observed between response groups. Conclusion In this retrospective surgical cohort, neoadjuvant chemotherapy plus PD-1 blockade was associated with encouraging pathological response rates, a high R0 resection rate, and manageable toxicity. Higher PD-L1 expression was associated with pathological response but not survival. Exploratory paired-tissue findings suggest that treatment-associated increases in intratumoral CD103 + CD8 + T-cell density may represent a response-associated immune feature requiring prospective validation.