Helicobacter pylori reversing the landscape of neoadjuvant immunotherapy for microsatellite stable gastric cancer: a multicenter cohort study.

Background: Microsatellite stable (MSS) gastric cancer (GC) is largely unresponsive to immunotherapy, presenting a persistent and formidable challenge in the field. Patients with advanced GC and Helicobacter pylori (H. pylori) infection have shown benefits from immunotherapy. However, it remains unreported whether neoadjuvant immunotherapy is beneficial for H. pylori-positive MSS GC patients.

Methods: This retrospective cohort study analyzed data from GC patients treated at three medical centers in China between January 1, 2014, and July 1, 2024. Patients with gastric adenocarcinoma or adenocarcinoma of the gastroesophageal junction underwent testing for H. pylori infection prior to receiving neoadjuvant therapy.

Results: In this retrospective analysis, those positive for H. pylori had a higher objective response rate of 63.77% (95% CI, 51.98-74.11%) compared to 47.73% (95% CI, 39.39-56.19%) in H. pylori-negative patients. Pathological complete remission was higher in H. pylori-positive patients at 17.39% (95% CI, 10.24-27.98%) versus 15.91% (95% CI, 10.65-23.10%). Logistic regression analysis revealed a strong correlation between H. pylori positivity and increased objective remission rate (P = 0.031, OR = 1.928, 95% CI 1.06-3.51). In H. pylori-positive MSS GC patients receiving neoadjuvant immunotherapy pCR rates can reach 27.27% (95% CI, 15.07-44.21%), much higher than the 8.33% (95% CI, 2.87-21.82%) in neoadjuvant chemotherapy patients. Survival analysis showed a 3-year OS rate of 74.2% (95% CI, 56.75-86.30%) in the H. pylori-positive group and 64.3% (95% CI, 51.20-75.55%) in the H. pylori-negative group, and the hazard ratio (HR) of these two groups was 0.50 (95% CI, 0.28-0.87; P <.001). Multivariable analysis for OS further showed the survival benefit of H. pylori, with HRs of 0.51 (95% CI, 0.29-0.91; P = 0.02).

Conclusions: H. pylori infection has emerged as a favorable factor for neoadjuvant immunotherapy in MSS GC, underscoring the importance of considering H. pylori status in preoperative treatment strategies.