小柯机器人

美国德克萨斯大学Lauren E. Colbert等研究人员发现，驻留在肿瘤中的乳酸杆菌通过乳酸盐诱导的新陈代谢重构赋予化疗抗性。相关论文于2023年10月19日在线发表在《癌细胞》杂志上。

研究人员采用深度微生物组测序、靶向细菌培养和体外检测相结合的方法来探索了影响宫颈癌患者化疗反应的肿瘤和肠道微生物组特征。研究人员发现，在肿瘤中发现的一种必须产L-乳酸的乳酸菌（Lactobacillus iners）与患者生存率下降有关，它能诱导宫颈癌细胞产生化疗和放疗耐药性，并导致肿瘤中的代谢重构或多种代谢途径的改变。

与其他身体部位共生的产L-乳酸菌基因组相似的乳酸菌也与结直肠癌、肺癌、头颈部癌和皮肤癌患者的存活率显著相关。这些研究结果表明，肿瘤微环境中的乳酸菌可改变肿瘤代谢和乳酸信号通路，导致治疗耐药性。乳酸菌可能成为各种癌症的治疗靶点。

据介绍，肿瘤微生物群能产生活性代谢物，影响癌细胞和免疫细胞的信号转导、新陈代谢和增殖。

附：英文原文

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

Author: Lauren E. Colbert, Molly B. El Alam, Rui Wang, Tatiana Karpinets, David Lo, Erica J. Lynn, Timothy A. Harris, Jacob H. Elnaggar, Kyoko Yoshida-Court, Katarina Tomasic, Julianna K. Bronk, Julie Sammouri, Ananta V. Yanamandra, Adilene V. Olvera, Lily G. Carlin, Travis Sims, Andrea Y. Delgado Medrano, Tatiana Cisneros Napravnik, Madison O’Hara, Daniel Lin, Chike O. Abana, Hannah X. Li, Patricia J. Eifel, Anuja Jhingran, Melissa Joyner, Lilie Lin, Lois M. Ramondetta, Andrew M. Futreal, Kathleen M. Schmeler, Geena Mathew, Stephanie Dorta-Estremera, Jianhua Zhang, Xiaogang Wu, Nadim J. Ajami, Matthew Wong, Cullen Taniguchi, Joseph F. Petrosino, K. Jagannadha Sastry, Pablo C. Okhuysen, Sara A. Martinez, Lin Tan, Iqbal Mahmud, Philip L. Lorenzi, Jennifer A. Wargo, Ann H. Klopp

Issue&Volume: 2023-10-19

Abstract: 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.

DOI: 10.1016/j.ccell.2023.09.012

Source: https://www.cell.com/cancer-cell/fulltext/S1535-6108(23)00328-8

Cancer Cell：《癌细胞》，创刊于2002年。隶属于细胞出版社，最新IF：38.585
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