Helicobacter pylori infection has a detrimental impact on the efficacy of cancer immunotherapies. Issue 3 (12th July 2021)

• Record Type: Journal Article
• Authors: Oster, Paul; Vaillant, Laurie; Riva, Erika; McMillan, Brynn; Begka, Christina; Truntzer, Caroline; Richard, Corentin; Leblond, Marine M; Messaoudene, Meriem; Machremi, Elisavet; Limagne, Emeric; Ghiringhelli, Francois; Routy, Bertrand; Verdeil, Gregory; Velin, Dominique
• Is Part Of: Gut. Volume 71:Issue 3(2022)
• Page Start: 457
• Page End: 466
• Publication Date: 2021-07-12
• Subjects: Helicobacter pylori -- cancer -- immunotherapy -- cancer immunobiology; Gastroenterology -- Periodicals; 616.33
• DOI: 10.1136/gutjnl-2020-323392
• Languages: English
• ISSNs: 0017-5749

Abstract

Abstract : Objective: In this study, we determined whether Helicobacter pylori ( H. pylori ) infection dampens the efficacy of cancer immunotherapies. Design: Using mouse models, we evaluated whether immune checkpoint inhibitors or vaccine-based immunotherapies are effective in reducing tumour volumes of H. pylori -infected mice. In humans, we evaluated the correlation between H. pylori seropositivity and the efficacy of the programmed cell death protein 1 (PD-1) blockade therapy in patients with non-small-cell lung cancer (NSCLC). Results: In mice engrafted with MC38 colon adenocarcinoma or B16-OVA melanoma cells, the tumour volumes of non-infected mice undergoing anticytotoxic T-lymphocyte-associated protein 4 and/or programmed death ligand 1 or anti-cancer vaccine treatments were significantly smaller than those of infected mice. We observed a decreased number and activation status of tumour-specific CD8 + T cells in the tumours of infected mice treated with cancer immunotherapies independent of the gut microbiome composition. Additionally, by performing an in vitro co-culture assay, we observed that dendritic cells of infected mice promote lower tumour-specific CD8 + T cell proliferation. We performed retrospective human clinical studies in two independent cohorts. In the Dijon cohort, H. pylori seropositivity was found to be associated with a decreased NSCLC patient survival on anti-PD-1 therapy. The survival median for H. pylori seropositive patients was 6.7 months compared with 15.4 months for seronegative patients (p=0.001). Additionally, in the Montreal cohort, H. pylori seropositivity was found to be associated with an apparent decrease of NSCLC patient progression-free survival on anti-PD-1 therapy. Conclusion: Our study unveils for the first time that the stomach microbiota affects the response to cancer immunotherapies and that H. pylori serology would be a powerful tool to personalize cancer immunotherapy treatment.