Tumor-resident Lactobacillus iners confer chemoradiation resistance through lactate-induced metabolic rewiring.

Female Humans Lactic Acid / metabolism Uterine Cervical Neoplasms / radiotherapy Lactobacillus / genetics Microbiota Tumor Microenvironment
cervical cancer chemoradiation lactate metabolism microbiome radiation

Journal

Cancer cell
ISSN: 1878-3686
Titre abrégé: Cancer Cell
Pays: United States
ID NLM: 101130617

Informations de publication

Date de publication:
13 11 2023
Historique:
received: 10 11 2022
revised: 01 07 2023
accepted: 25 09 2023
medline: 16 11 2023
pubmed: 21 10 2023
entrez: 20 10 2023
Statut: ppublish

Résumé

Tumor microbiota can produce active metabolites that affect cancer and immune cell signaling, metabolism, and proliferation. Here, we explore tumor and gut microbiome features that affect chemoradiation response in patients with cervical cancer using a combined approach of deep microbiome sequencing, targeted bacterial culture, and in vitro assays. We identify that an obligate L-lactate-producing lactic acid bacterium found in tumors, Lactobacillus iners, is associated with decreased survival in patients, induces chemotherapy and radiation resistance in cervical cancer cells, and leads to metabolic rewiring, or alterations in multiple metabolic pathways, in tumors. Genomically similar L-lactate-producing lactic acid bacteria commensal to other body sites are also significantly associated with survival in colorectal, lung, head and neck, and skin cancers. Our findings demonstrate that lactic acid bacteria in the tumor microenvironment can alter tumor metabolism and lactate signaling pathways, causing therapeutic resistance. Lactic acid bacteria could be promising therapeutic targets across cancer types.

Identifiants

DOI: 10.1016/j.ccell.2023.09.012 PMID: 37863066
pubmed: 37863066
pii: S1535-6108(23)00328-8
doi: 10.1016/j.ccell.2023.09.012
pii:
doi:

Substances chimiques

Lactic Acid 33X04XA5AT

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, U.S. Gov't, Non-P.H.S. Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1945-1962.e11

Subventions

Organisme : NCI NIH HHS
ID : P30 CA016672
Pays : United States
Organisme : NCI NIH HHS
ID : U54 CA096300
Pays : United States

Informations de copyright

Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests L.E.C. reports grants from American Society for Clinical Oncology, Radiology Society of North America, National Institutes of Health, and MD Anderson Cancer Center during the conduct of the study. A.J. reports personal fees from Genentech during the conduct of the study, as well as personal fees from Genentech outside the submitted work. L.L. reports other support from AstraZeneca and Pfizer, and grants from NCI outside the submitted work. J.A.W. reports other support from Micronoma during the conduct of the study, as well as other support from Imedex, Dava Oncology, Illumina, and PeerView outside the submitted work. P.O. reports Faculty grant/research support from Merck Sharp and Dohme Corp, Deinove Pharmaceuticals, Summit Pharmaceuticals, Melinta Pharmaceuticals, and Napo Pharmaceutical, in addition to consultant work with Napo Pharmaceutical, Ferring Pharmaceutical, Summit Pharmaceutical, and SNIPR Biome Company, all outside of the submitted work.

Auteurs

Lauren E Colbert (LE)

Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. Electronic address: lcolbert@mdanderson.org.

Molly B El Alam (MB)

Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

Rui Wang (R)

Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

Tatiana Karpinets (T)

Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

David Lo (D)

Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

Erica J Lynn (EJ)

Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

Timothy A Harris (TA)

Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

Jacob H Elnaggar (JH)

Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; LSU School of Medicine, Louisiana State University, Baton Rouge, LA 70803, USA.

Kyoko Yoshida-Court (K)

Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

Katarina Tomasic (K)

Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

Julianna K Bronk (JK)

Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

Julie Sammouri (J)

Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

Ananta V Yanamandra (AV)

Department of Translational and Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

Adilene V Olvera (AV)

Departments of Infectious Diseases, Infection Control and Employee Health, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

Lily G Carlin (LG)

Departments of Infectious Diseases, Infection Control and Employee Health, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

Travis Sims (T)

Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

Andrea Y Delgado Medrano (AY)

Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

Tatiana Cisneros Napravnik (TC)

Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

Madison O'Hara (M)

Department of Thoracic Head and Neck Medical Oncology at The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

Daniel Lin (D)

Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

Chike O Abana (CO)

Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

Hannah X Li (HX)

Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

Patricia J Eifel (PJ)

Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

Anuja Jhingran (A)

Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

Melissa Joyner (M)

Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

Lilie Lin (L)

Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

Lois M Ramondetta (LM)

Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

Andrew M Futreal (AM)

Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

Kathleen M Schmeler (KM)

Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

Geena Mathew (G)

Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

Stephanie Dorta-Estremera (S)

Department of Microbiology and Medical Zoology, University of Puerto Rico, San Juan, PR 00921, USA.

Jianhua Zhang (J)

Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

Xiaogang Wu (X)

Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

Nadim J Ajami (NJ)

Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Platform for Innovative Microbiome and Translational Research, Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

Matthew Wong (M)

Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Platform for Innovative Microbiome and Translational Research, Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

Cullen Taniguchi (C)

Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

Joseph F Petrosino (JF)

Department of Molecular Virology and Microbiology, The Alkek Center for Metagenomics and Microbiome Research, Baylor College of Medicine, Houston, TX 77030, USA.

K Jagannadha Sastry (KJ)

Department of Thoracic Head and Neck Medical Oncology at The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

Pablo C Okhuysen (PC)

Departments of Infectious Diseases, Infection Control and Employee Health, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

Sara A Martinez (SA)

Metabolomics Core Facility, Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

Lin Tan (L)

Metabolomics Core Facility, Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

Iqbal Mahmud (I)

Metabolomics Core Facility, Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

Philip L Lorenzi (PL)

Metabolomics Core Facility, Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

Jennifer A Wargo (JA)

Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; LSU School of Medicine, Louisiana State University, Baton Rouge, LA 70803, USA; Platform for Innovative Microbiome and Translational Research, Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

Ann H Klopp (AH)

Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Tumor-resident Lactobacillus iners confer...
questionsmedicales.fr › Composés chimiques organiques › Acides carboxyliques › Hydroxyacides › Lactates › Acide lactique › Tumor-resident Lactobacillus iners confer...
questionsmedicales.fr › Maladies urogénitales › Tumeurs de l'appareil urogénital › Tumeurs de l'appareil génital féminin › Tumeurs de l'utérus › Tumeurs du col de l'utérus › Tumor-resident Lactobacillus iners confer...
questionsmedicales.fr › Bactéries › Bactéries à Gram positif › Lactobacillales › Lactobacillaceae › Lactobacillus › Tumor-resident Lactobacillus iners confer...
questionsmedicales.fr › Environnement et santé publique › Environnement › Écosystème › Biodiversité › Biote › Microbiote › Tumor-resident Lactobacillus iners confer...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Microenvironnement cellulaire › Microenvironnement tumoral › Tumor-resident Lactobacillus iners confer...