TY - JOUR T1 - <em>Helicobacter pylori</em> infection has a detrimental impact on the efficacy of cancer immunotherapies JF - Gut JO - Gut SP - 457 LP - 466 DO - 10.1136/gutjnl-2020-323392 VL - 71 IS - 3 AU - Paul Oster AU - Laurie Vaillant AU - Erika Riva AU - Brynn McMillan AU - Christina Begka AU - Caroline Truntzer AU - Corentin Richard AU - Marine M Leblond AU - Meriem Messaoudene AU - Elisavet Machremi AU - Emeric Limagne AU - Francois Ghiringhelli AU - Bertrand Routy AU - Gregory Verdeil AU - Dominique Velin Y1 - 2022/03/01 UR - http://gut.bmj.com/content/71/3/457.abstract N2 - 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.Data are available upon reasonable request. ER -