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
{"title":"幽门螺杆菌与胃肠癌免疫疗法","authors":"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","DOIUrl":null,"url":null,"abstract":"<p><em>Helicobacter pylori</em> 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 <sup>13</sup>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, <em>H. pylori</em>-positive patients exhibited significantly longer immune-related progression-free survival (irPFS) compared with <em>H. pylori</em>-negative patients (6.97 months vs. 5.03 months, <em>P</em><0.001; hazards ratio [HR], 0.76; 95% confidence interval [CI], 0.62–0.95; <em>P</em>=0.015). Moreover, the <em>H. pylori</em>-positive group demonstrated a trend of 4-months longer median immune-related overall survival (irOS) than the <em>H. pylori</em>-negative group. <em>H. pylori</em>-positive GC displayed higher densities of PD-L1<sup>+</sup> cells and non-exhausted CD8<sup>+</sup> T cells, indicative of a \"hot\" tumor microenvironment. Transcriptomic analysis revealed that <em>H. pylori</em>-positive GC shared similar molecular characteristics to immunotherapy-sensitive GC. However, <em>H. pylori</em>-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 <em>H. pylori</em>-negative patients (16.13 months vs. not reached, <em>P</em>=0.042; HR, 2.26; 95% CI, 1.13–4.50; <em>P</em>=0.021 and 5.57 months vs. 6.97 months, <em>P</em>=0.029; HR, 1.59; 95% CI, 1.14–2.23; <em>P</em>=0.006, respectively). The difference of irOS between <em>H. pylori</em>-positive and negative patients had the same trend to that between dMMR/MSI-H colorectal adenocarcinoma and ESCC patients. We also identified a trend of shorter irPFS and irOS in <em>H. pylori</em>-positive liver cancer and pancreatic cancer patients. In summary, our findings supported that <em>H. pylori</em> infection is a beneficial factor for GC immunotherapy by shaping \"hot\" tumor microenvironment. However, in dMMR/MSI-H colorectal adenocarcinoma and ESCC patients, <em>H. pylori</em> adversely affects the efficacy of immunotherapy.</p>","PeriodicalId":36121,"journal":{"name":"The Innovation","volume":"8 1","pages":""},"PeriodicalIF":33.2000,"publicationDate":"2024-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Helicobacter pylori and immunotherapy for gastrointestinal cancer\",\"authors\":\"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\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><em>Helicobacter pylori</em> 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 <sup>13</sup>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, <em>H. pylori</em>-positive patients exhibited significantly longer immune-related progression-free survival (irPFS) compared with <em>H. pylori</em>-negative patients (6.97 months vs. 5.03 months, <em>P</em><0.001; hazards ratio [HR], 0.76; 95% confidence interval [CI], 0.62–0.95; <em>P</em>=0.015). Moreover, the <em>H. pylori</em>-positive group demonstrated a trend of 4-months longer median immune-related overall survival (irOS) than the <em>H. pylori</em>-negative group. <em>H. pylori</em>-positive GC displayed higher densities of PD-L1<sup>+</sup> cells and non-exhausted CD8<sup>+</sup> T cells, indicative of a \\\"hot\\\" tumor microenvironment. Transcriptomic analysis revealed that <em>H. pylori</em>-positive GC shared similar molecular characteristics to immunotherapy-sensitive GC. However, <em>H. pylori</em>-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 <em>H. pylori</em>-negative patients (16.13 months vs. not reached, <em>P</em>=0.042; HR, 2.26; 95% CI, 1.13–4.50; <em>P</em>=0.021 and 5.57 months vs. 6.97 months, <em>P</em>=0.029; HR, 1.59; 95% CI, 1.14–2.23; <em>P</em>=0.006, respectively). The difference of irOS between <em>H. pylori</em>-positive and negative patients had the same trend to that between dMMR/MSI-H colorectal adenocarcinoma and ESCC patients. We also identified a trend of shorter irPFS and irOS in <em>H. pylori</em>-positive liver cancer and pancreatic cancer patients. In summary, our findings supported that <em>H. pylori</em> infection is a beneficial factor for GC immunotherapy by shaping \\\"hot\\\" tumor microenvironment. However, in dMMR/MSI-H colorectal adenocarcinoma and ESCC patients, <em>H. pylori</em> adversely affects the efficacy of immunotherapy.</p>\",\"PeriodicalId\":36121,\"journal\":{\"name\":\"The Innovation\",\"volume\":\"8 1\",\"pages\":\"\"},\"PeriodicalIF\":33.2000,\"publicationDate\":\"2024-01-08\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"The Innovation\",\"FirstCategoryId\":\"95\",\"ListUrlMain\":\"https://doi.org/10.1016/j.xinn.2023.100561\",\"RegionNum\":1,\"RegionCategory\":\"综合性期刊\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"MULTIDISCIPLINARY SCIENCES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"The Innovation","FirstCategoryId":"95","ListUrlMain":"https://doi.org/10.1016/j.xinn.2023.100561","RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MULTIDISCIPLINARY SCIENCES","Score":null,"Total":0}
Helicobacter pylori and immunotherapy for gastrointestinal cancer
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 vs. 5.03 months, P<0.001; hazards 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 non-exhausted CD8+ T cells, indicative of a "hot" tumor microenvironment. Transcriptomic analysis revealed that H. pylori-positive GC shared similar molecular characteristics to 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 vs. not reached, P=0.042; HR, 2.26; 95% CI, 1.13–4.50; P=0.021 and 5.57 months vs. 6.97 months, P=0.029; HR, 1.59; 95% CI, 1.14–2.23; P=0.006, respectively). The difference of irOS between H. pylori-positive and negative patients had the same trend to 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 microenvironment. However, in dMMR/MSI-H colorectal adenocarcinoma and ESCC patients, H. pylori adversely affects the efficacy of immunotherapy.
期刊介绍：
The Innovation is an interdisciplinary journal that aims to promote scientific application. It publishes cutting-edge research and high-quality reviews in various scientific disciplines, including physics, chemistry, materials, nanotechnology, biology, translational medicine, geoscience, and engineering. The journal adheres to the peer review and publishing standards of Cell Press journals.
The Innovation is committed to serving scientists and the public. It aims to publish significant advances promptly and provides a transparent exchange platform. The journal also strives to efficiently promote the translation from scientific discovery to technological achievements and rapidly disseminate scientific findings worldwide.
Indexed in the following databases, The Innovation has visibility in Scopus, Directory of Open Access Journals (DOAJ), Web of Science, Emerging Sources Citation Index (ESCI), PubMed Central, Compendex (previously Ei index), INSPEC, and CABI A&I.
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