Titre
Helicobacter pylori infection has a detrimental impact on the efficacy of cancer immunotherapies.
Type
article
Institution
UNIL/CHUV/Unisanté + institutions partenaires
Périodique
Auteur(s)
Oster, P.
Auteure/Auteur
Vaillant, L.
Auteure/Auteur
Riva, E.
Auteure/Auteur
McMillan, B.
Auteure/Auteur
Begka, C.
Auteure/Auteur
Truntzer, C.
Auteure/Auteur
Richard, C.
Auteure/Auteur
Leblond, M.M.
Auteure/Auteur
Messaoudene, M.
Auteure/Auteur
Machremi, E.
Auteure/Auteur
Limagne, E.
Auteure/Auteur
Ghiringhelli, F.
Auteure/Auteur
Routy, B.
Auteure/Auteur
Verdeil, G.
Auteure/Auteur
Velin, D.
Auteure/Auteur
Liens vers les personnes
Liens vers les unités
ISSN
1468-3288
Statut éditorial
Publié
Date de publication
2022-03
Volume
71
Numéro
3
Première page
457
Dernière page/numéro d’article
466
Peer-reviewed
Oui
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Publication Status: ppublish
Résumé
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.
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.
Sujets
PID Serval
serval:BIB_142E8F1FCE05
PMID
Open Access
Oui
Date de création
2021-07-15T13:21:54.981Z
Date de création dans IRIS
2025-05-20T17:40:44Z
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Nom
34253574_BIB_142E8F1FCE05.pdf
Version du manuscrit
preprint
Licence
https://creativecommons.org/licenses/by-nc/4.0
Taille
2.18 MB
Format
Adobe PDF
PID Serval
serval:BIB_142E8F1FCE05.P001
Somme de contrôle
(MD5):5ac164ea48c4f49aaba82763b102a4b2