<i>Helicobacter pylori</i> infection has a detrimental impact on the efficacy of cancer immunotherapies.

Abstract

In this study, we determined whether <i>Helicobacter pylori</i> (<i>H. pylori</i>) infection dampens the efficacy of cancer immunotherapies. Using mouse models, we evaluated whether immune checkpoint inhibitors or vaccine-based immunotherapies are effective in reducing tumour volumes of <i>H. pylori</i>-infected mice. In humans, we evaluated the correlation between <i>H. pylori</i> seropositivity and the efficacy of the programmed cell death protein 1 (PD-1) blockade therapy in patients with non-small-cell lung cancer (NSCLC). 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, <i>H. pylori</i> seropositivity was found to be associated with a decreased NSCLC patient survival on anti-PD-1 therapy. The survival median for <i>H. pylori</i> seropositive patients was 6.7 months compared with 15.4 months for seronegative patients (p=0.001). Additionally, in the Montreal cohort, <i>H. pylori</i> seropositivity was found to be associated with an apparent decrease of NSCLC patient progression-free survival on anti-PD-1 therapy. Our study unveils for the first time that the stomach microbiota affects the response to cancer immunotherapies and that <i>H. pylori</i> serology would be a powerful tool to personalize cancer immunotherapy treatment.