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

The Innovation > 2024 Vol. 5 > No. 2

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Helicobacter pylori and immunotherapy for gastrointestinal cancer

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

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³These authors contributed equally
Corresponding author: shenlin@bjmu.edu.cn
Received Date: August 15, 2023

Accepted Date: December 29, 2023

Published Online: January 08, 2024

The Innovation 5(2), https://doi.org/10.1016/j.xinn.2023.100561 | Cite this article

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PUBLIC SUMMARY

PUBLIC SUMMARY
1. ■ Helicobacter pylori infection is a favorable factor for gastric cancer immunotherapy by shaping the "hot" tumor microenvironment.
2. ■ H. pylori infection is unfavorable for immunotherapy in DNA mismatch repair-deficient/microsatellite instability-high colon adenocarcinoma and esophageal squamous cell cancer.
3. ■ This study highlights the importance of the test for H. pylori infection in cancer patients treated with immunotherapy.

ABSTRACT

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.

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ABOUT THIS ARTICLE

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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. Helicobacter pylori and immunotherapy for gastrointestinal cancer[J]. The Innovation, 2024, 5(2). https://doi.org/10.1016/j.xinn.2023.100561

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. Helicobacter pylori and immunotherapy for gastrointestinal cancer[J]. The Innovation, 2024, 5(2). https://doi.org/10.1016/j.xinn.2023.100561

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