Helicobacter pylori and immunotherapy for gastrointestinal cancer
© 2024 The Authors..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:5 |
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| Enthalten in: |
Innovation (Cambridge (Mass.)) - 5(2024), 2 vom: 04. Feb., Seite 100561 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Jia, Keren [VerfasserIn] |
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| Links: |
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| Themen: |
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| Anmerkungen: |
Date Revised 22.02.2024 published: Electronic-eCollection Citation Status PubMed-not-MEDLINE |
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| doi: |
10.1016/j.xinn.2023.100561 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM368698017 |
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| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 700 | 1 | |a Chen, Yang |e verfasserin |4 aut | |
| 700 | 1 | |a Xie, Yi |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Xicheng |e verfasserin |4 aut | |
| 700 | 1 | |a Hu, Yajie |e verfasserin |4 aut | |
| 700 | 1 | |a Sun, Yu |e verfasserin |4 aut | |
| 700 | 1 | |a Cao, Yanshuo |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Liyan |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Yakun |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Zhenghang |e verfasserin |4 aut | |
| 700 | 1 | |a Lu, Zhihao |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Jian |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Xiaotian |e verfasserin |4 aut | |
| 700 | 1 | |a Shen, Lin |e verfasserin |4 aut | |
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| 773 | 1 | 8 | |g volume:5 |g year:2024 |g number:2 |g day:04 |g month:02 |g pages:100561 |
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