Helicobacter pylori infection is associated with the risk of gastrointestinal(GI)cancers;however,its impact on immunotherapy for GI cancers remains uncertain.In this study,we included 10,122 patients who underwent ^(1...Helicobacter pylori infection is associated with the risk of gastrointestinal(GI)cancers;however,its impact on immunotherapy for GI cancers remains uncertain.In this study,we included 10,122 patients who underwent ^(13)C-urea breath tests.Among 636 patients with Epstein-Barr virus–negative microsatellite-stable gastric cancer(GC)who were treated with anti-PD-1/PD-L1 therapy,H.pylori–positive patients exhibited significantly longer immune-related progression-free survival(irPFS)compared with H.pylori–negative patients(6.97 months versus 5.03 months,p<0.001,hazard ratio[HR]0.76,95%confidence interval[CI]0.62–0.95,p=0.015).Moreover,the H.pylori–positive group demonstrated a trend of 4 months longer median immune-related overall survival(irOS)than the H.pylori–negative group.H.pylori–positive GC displayed higher densities of PD-L1+cells and nonexhausted CD8+T cells,indicative of a“hot”tumor microenvironment.Transcriptomic analysis revealed that H.pylori–positive GC shared molecular characteristics similar to those of immunotherapy-sensitive GC.However,H.pylori–positive patients with DNA mismatch repair–deficient(dMMR)/microsatellite instability–high(MSI-H)colorectal adenocarcinoma and esophageal squamous cell carcinoma(ESCC)had shorter irPFS compared with H.pylori–negative patients(16.13 months versus not reached,p=0.042,HR 2.26,95%CI 1.13–4.50,p=0.021 and 5.57 months versus 6.97 months,p=0.029,HR 1.59,95%CI 1.14–2.23,p=0.006,respectively).The difference in irOS between H.pylori–positive and–negative patients had the same trend as that between dMMR/MSI-H colorectal adenocarcinoma and ESCC patients.We also identified a trend of shorter irPFS and irOS in H.pylori–positive liver cancer and pancreatic cancer patients.In summary,our findings supported that H.pylori infection is a beneficial factor for GC immunotherapy by shaping hot tumor microenvironments.However,in dMMR/MSI-H colorectal adenocarcinoma and ESCC patients,H.pylori adversely affects the efficacy of immunotherapy.展开更多
基金This work was supported by the National Natural Science Foundation of China(82203881 and U22A20327)the Beijing Natural Science Foundation(7222021 and Z200015)+2 种基金the Beijing Hospitals Authority Youth Programme(QML20231115)the Clinical Medicine Plus X-Young Scholars Project of Peking University(PKU2023LCXQ041)the Beijing Science and Technology Plan Project(Z231100007423009)。
文摘Helicobacter pylori infection is associated with the risk of gastrointestinal(GI)cancers;however,its impact on immunotherapy for GI cancers remains uncertain.In this study,we included 10,122 patients who underwent ^(13)C-urea breath tests.Among 636 patients with Epstein-Barr virus–negative microsatellite-stable gastric cancer(GC)who were treated with anti-PD-1/PD-L1 therapy,H.pylori–positive patients exhibited significantly longer immune-related progression-free survival(irPFS)compared with H.pylori–negative patients(6.97 months versus 5.03 months,p<0.001,hazard ratio[HR]0.76,95%confidence interval[CI]0.62–0.95,p=0.015).Moreover,the H.pylori–positive group demonstrated a trend of 4 months longer median immune-related overall survival(irOS)than the H.pylori–negative group.H.pylori–positive GC displayed higher densities of PD-L1+cells and nonexhausted CD8+T cells,indicative of a“hot”tumor microenvironment.Transcriptomic analysis revealed that H.pylori–positive GC shared molecular characteristics similar to those of immunotherapy-sensitive GC.However,H.pylori–positive patients with DNA mismatch repair–deficient(dMMR)/microsatellite instability–high(MSI-H)colorectal adenocarcinoma and esophageal squamous cell carcinoma(ESCC)had shorter irPFS compared with H.pylori–negative patients(16.13 months versus not reached,p=0.042,HR 2.26,95%CI 1.13–4.50,p=0.021 and 5.57 months versus 6.97 months,p=0.029,HR 1.59,95%CI 1.14–2.23,p=0.006,respectively).The difference in irOS between H.pylori–positive and–negative patients had the same trend as that between dMMR/MSI-H colorectal adenocarcinoma and ESCC patients.We also identified a trend of shorter irPFS and irOS in H.pylori–positive liver cancer and pancreatic cancer patients.In summary,our findings supported that H.pylori infection is a beneficial factor for GC immunotherapy by shaping hot tumor microenvironments.However,in dMMR/MSI-H colorectal adenocarcinoma and ESCC patients,H.pylori adversely affects the efficacy of immunotherapy.
