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

Autor:	Colbert LE; Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. Electronic address: lcolbert@mdanderson.org., El Alam MB; Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA., Wang R; Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA., Karpinets T; Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA., Lo D; Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA., Lynn EJ; Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA., Harris TA; Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA., 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., Yoshida-Court K; Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA., Tomasic K; Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA., Bronk JK; Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA., Sammouri J; Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA., Yanamandra AV; Department of Translational and Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA., Olvera AV; Departments of Infectious Diseases, Infection Control and Employee Health, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA., Carlin LG; Departments of Infectious Diseases, Infection Control and Employee Health, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA., Sims T; Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA., Delgado Medrano AY; Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA., Napravnik TC; Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA., O'Hara M; Department of Thoracic Head and Neck Medical Oncology at The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA., Lin D; Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA., Abana CO; Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA., Li HX; Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA., Eifel PJ; Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA., Jhingran A; Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA., Joyner M; Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA., Lin L; Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA., Ramondetta LM; Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA., Futreal AM; Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA., Schmeler KM; Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA., Mathew G; Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA., Dorta-Estremera S; Department of Microbiology and Medical Zoology, University of Puerto Rico, San Juan, PR 00921, USA., Zhang J; Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA., Wu X; Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA., 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., 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., Taniguchi C; Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA., Petrosino JF; Department of Molecular Virology and Microbiology, The Alkek Center for Metagenomics and Microbiome Research, Baylor College of Medicine, Houston, TX 77030, USA., Sastry KJ; Department of Thoracic Head and Neck Medical Oncology at The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA., Okhuysen PC; Departments of Infectious Diseases, Infection Control and Employee Health, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA., Martinez SA; Metabolomics Core Facility, Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA., Tan L; Metabolomics Core Facility, Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA., Mahmud I; Metabolomics Core Facility, Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA., Lorenzi PL; Metabolomics Core Facility, Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA., 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., Klopp AH; Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Jazyk:	angličtina
Zdroj:	Cancer cell [Cancer Cell] 2023 Nov 13; Vol. 41 (11), pp. 1945-1962.e11. Date of Electronic Publication: 2023 Oct 19.
DOI:	10.1016/j.ccell.2023.09.012
Abstrakt:	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. Competing Interests: 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. (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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