Helicobacter pylori and immunotherapy for gastrointestinal cancer  

作　　者：Keren Jia Yang Chen Yi Xie Xicheng Wang Yajie Hu Yu Sun Yanshuo Cao Liyan Zhang Yakun Wang Zhenghang Wang Zhihao Lu Jian Li Xiaotian Zhang Lin Shen 

机构地区：[1]Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing),Department of Gastrointestinal Oncology,Peking University Cancer Hospital&Institute,Beijing 100142,China [2]Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing),Department of Pathology,Peking University Cancer Hospital&Institute,Beijing 100142,China

出　　处：《The Innovation》2024年第2期51-60,共10页创新（英文）

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);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)。

摘　　要：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.

关 键 词：IMMUNOTHERAPY GASTROINTESTINAL PYLORI 

分 类 号：R573[医药卫生—消化系统] R73[医药卫生—内科学]