OUP accepted manuscript

Paradoxically, Helicobacter pylori-positive (HP+) advanced gastric cancer patients have a better prognosis than those who are HP-negative (HP-). Immunologic and statistical analyses can be used to verify whether systemic mechanisms modulated by HP are involved in this more favorable outcome.A total of 658 advanced gastric cancer patients who underwent gastrectomy were enrolled. HP infection, mismatch repair, programmed death-ligand 1 (PD-L1), and CD4/CD8 proteins, and microsatellite instability were analyzed. Overall survival (OS) and relapse free survival (RFS) rates were analyzed after stratifying clinicopathological factors. Cox proportional hazards regression analysis was performed to identify independent prognostic factors.Among 491 cases that were analyzed, 175 (36%) and 316 (64%) cases were HP+ and HP⁻, respectively. Analysis of RFS indicated an interaction of HP status among the subgroups for S-1 dose (Pinteraction=0.0487) and PD-L1 (P = .016). HP+ patients in the PD-L1⁻ group had significantly higher five-year OS and RFS than HP- patients (81% vs. 68%; P = .0011; HR 0.477; 95% CI, 0.303-0.751 and 76% vs. 63% P = .0011; HR 0.508; 95% CI, 0.335-0.771, respectively). The five-year OS and RFS was also significantly higher for HP+ compared to HP- patients in the PD-L1-/S-1-reduced group (86% vs. 46%; P = .0014; HR 0.205; 95% CI, 0.07-0.602 and 83% vs. 34%; P = .001; HR 0.190; 95% CI, 0.072-0.498, respectively). Thus, HP status was identified as one of the most potentially important independent factors to predict prolonged survival.This retrospective study suggests that an HP-modulated host immune system may contribute to prolonged survival in the absence of immune escape mechanisms of gastric cancer.