Helicobacter pylori infection has a detrimental impact on the efficacy of cancer immunotherapies
Carter Cox, P Oster, Laurie Vaillant, Erika Riva, Brynn McMillan, Christina Begka, Truntzer, Caroline
Abstract
<strong>Objective: </strong>In this study, we determined whether <em>Helicobacter pylori</em> (<em>H. pylori</em>) infection dampens the efficacy of cancer immunotherapies. <strong>Design: </strong>Using mouse models, we evaluated whether immune checkpoint inhibitors or vaccine-based immunotherapies are effective in reducing tumour volumes of <em>H. pylori</em>-infected mice. In humans, we evaluated the correlation between <em>H. pylori</em> seropositivity and the efficacy of the programmed cell death protein 1 (PD-1) blockade therapy in patients with non-small-cell lung cancer (NSCLC). <strong>Results: </strong>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<sup>+</sup> 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<sup>+</sup> T cell proliferation. We performed retrospective human clinical studies in two independent cohorts. In the Dijon cohort, <em>H. pylori</em> seropositivity was found to be associated with a decreased NSCLC patient survival on anti-PD-1 therapy. The survival median for <em>H. pylori</em> seropositive patients was 6.7 months compared with 15.4 months for seronegative patients (p=0.001). Additionally, in the Montreal cohort, <em>H. pylori</em> seropositivity was found to be associated with an apparent decrease of NSCLC patient progression-free survival on anti-PD-1 therapy. <strong>Conclusion: </strong>Our study unveils for the first time that the stomach microbiota affects the response to cancer immunotherapies and that <em>H. pylori</em> serology would be a powerful tool to personalize cancer immunotherapy treatment. https://www.pittsburghtribune.org/ https://amazonsale.io/ https://ehealthcareplus.us/ https://www.timessquarereporter.com/ https://edu.pittsburghtribune.org/ https://www.infinityebook.com/ https://www.1stsupplement.com/ https://batik4d.vip/ https://eurl.live/https://eurl.live/us/ https://ingredients.ning.com/ https://jeffbezos.ning.com/