Clinical response of immunotherapy targeting programmed cell death receptor 1/programmed cell death ligand 1 in advanced signet-ring-cell gastric cancer

Background The clinical benefit of PD-1/PD-L1–based immunotherapy in gastric signet ring cell carcinoma (GSRCC) remains unclear. This study evaluated the efficacy of first-line immunotherapy in advanced GSRCC.Methods This single-center retrospective cohort study assessed the clinical response of patients with advanced GC diagnosed from November 2019 to January 2025 after receiving first-line immunotherapy combined with chemotherapy and/or target therapy, concurrently comparing therapeutic outcomes in GSRCC and non-GSRCC cohorts.Results This study included 230 patients, with objective response rate (ORR) achieving 43.9%. Among the 150 non-GSRCC patients, the ORR was 50.7%, compared to 31.3% in the 80 GSRCC patients. Non-GSRCC patients had longer median progression-free survival (PFS: 10.0 vs 7.9 months; p = 0.002) and overall survival (OS: 17.4 vs 15.3 months; p = 0.039). Peritoneal metastasis was independently associated with rapid progression and poor survival (HR 2.63, 95% CI 1.52–5.53; p = 0.001). Among GSRCC patients, those with peritoneal metastasis had significantly shorter PFS (6.6 vs 13.6 months; p < 0.001) and OS (11.0 vs 19.4 months; p = 0.001).Conclusions The findings suggest that GSRCC is associated with resistance to immunotherapy in advanced GC. Furthermore, peritoneal metastasis is significantly associated with poor prognosis in GSRCC patients.