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

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.
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.
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).
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.
Gastric signet ring cell carcinoma (GSRCC) is a special type of stomach cancer that behaves differently from other forms of the disease. Because of its unique features, doctors have long questioned whether modern immunotherapy treatments, which work by helping the immune system attack cancer – are as effective for GSRCC as they are for other stomach cancers. In this study, we reviewed 230 patients with advanced stomach cancer who received immunotherapy as their first treatment. We compared outcomes between patients with GSRCC and those with non-GSRCC. Our results showed that patients with GSRCC responded less well to immunotherapy and generally had shorter survival times. One important finding was that cancer spreading to the abdominal lining (peritoneal metastasis) strongly influenced treatment success. GSRCC patients with this type of spread had much shorter survival, suggesting they may require different treatment strategies. We also examined several common clinical features that doctors typically use to estimate treatment response. While these features helped explain outcomes in other stomach cancer patients, they did not fully clarify why GSRCC patients responded less effectively. This indicates that GSRCC may have unique biological characteristics that are not captured by current clinical indicators. Overall, our findings highlight the need for more personalized treatment approaches and further research to improve care for patients with this challenging type of stomach cancer.