Helicobacter pylori infection has a detrimental impact on the efficacy of cancer immunotherapies.

Details

Serval ID
serval:BIB_142E8F1FCE05
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Helicobacter pylori infection has a detrimental impact on the efficacy of cancer immunotherapies.
Journal
Gut
Author(s)
Oster P., Vaillant L., Riva E., McMillan B., Begka C., Truntzer C., Richard C., Leblond M.M., Messaoudene M., Machremi E., Limagne E., Ghiringhelli F., Routy B., Verdeil G., Velin D.
ISSN
1468-3288 (Electronic)
ISSN-L
0017-5749
Publication state
In Press
Peer-reviewed
Oui
Language
english
Notes
Publication types: Journal Article
Publication Status: aheadofprint
Abstract
In this study, we determined whether Helicobacter pylori (H. pylori) 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 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).
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, 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.
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.
Keywords
Helicobacter pylori, cancer, cancer immunobiology, immunotherapy
Pubmed
Open Access
Yes
Create date
15/07/2021 15:21
Last modification date
23/07/2021 6:38
Usage data