Helicobacter pylori and immunotherapy for gastrointestinal cancer

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

doi:10.1016/j.xinn.2023.100561

Helicobacter pylori and immunotherapy for gastrointestinal cancer

Innovation (Camb). 2024 Jan 8;5(2):100561. doi: 10.1016/j.xinn.2023.100561. eCollection 2024 Mar 4.

Authors

Keren Jia¹, Yang Chen¹, Yi Xie¹, Xicheng Wang¹, Yajie Hu², Yu Sun², Yanshuo Cao¹, Liyan Zhang¹, Yakun Wang¹, Zhenghang Wang¹, Zhihao Lu¹, Jian Li¹, Xiaotian Zhang¹, Lin Shen¹

Affiliations

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.

Abstract

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 ¹³C-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.