Esophagus to Small Intestine
Gut. 2022;71(3):457–66
Helicobacter pylori infection has a detrimental impact on the efficacy of cancer immunotherapies
Objective: In this study, it was determined whether Helicobacter pylori infection dampens the efficacy of cancer immunotherapies.
Design: Using mouse models, the authors evaluated whether immune checkpoint inhibitors or vaccine-based immunotherapies are effective in reducing tumor volumes of H. pylori-infected mice. In humans, they 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 tumor volumes of non-infected mice undergoing anti-cytotoxic T-lymphocyte-associated protein 4 and/or programmed death ligand 1 or anti-cancer vaccine treatments were significantly smaller than those of infected mice. A decreased number and activation status of tumor-specific CD8+ T cells was observed in the tumors of infected mice treated with cancer immunotherapies independent of the gut microbiome composition. Additionally, by performing an in vitro co-culture assay, it was observed that dendritic cells of infected mice promote lower tumor-specific CD8+ T cell proliferation. The authors performed retrospective human clinical studies in 2 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: This study unveils for the first time that the stomach microbiota affects the response to cancer immunotherapies and that Helicobacter pylori serology would be a powerful tool to personalize cancer immunotherapy treatment.