@article{f13563cc07524fbbb311d1d4e0286df8,
title = "Gut microbial metabolites facilitate anticancer therapy efficacy by modulating cytotoxic CD8+ T cell immunity",
abstract = "Recent studies in both mice and humans have suggested that gut microbiota could modulate tumor responsiveness to chemo- or immunotherapies. However, the underlying mechanism is not clear yet. Here, we found that gut microbial metabolites, especially butyrate, could promote the efficacy of oxaliplatin by modulating CD8+ T cell function in the tumor microenvironment. Butyrate treatment directly boosted the antitumor cytotoxic CD8+ T cell responses both in vitro and in vivo in an ID2-dependent manner by promoting the IL-12 signaling pathway. In humans, the oxaliplatin responder cancer patients exhibited a higher amount of serum butyrate than did non-responders, which could also increase ID2 expression and function of human CD8+ T cells. Together, our findings suggest that the gut microbial metabolite butyrate could promote antitumor therapeutic efficacy through the ID2-dependent regulation of CD8+ T cell immunity, indicating that gut microbial metabolites could be effective as a part of cancer therapy.",
keywords = "CD8+ T cell, ID2, IL-12, antitumor therapy efficacy, butyrate, gut microbial metabolites",
author = "Yao He and Liuhui Fu and Yiping Li and Wenyan Wang and Mingli Gong and Jing Zhang and Xin Dong and Jiaoyan Huang and Quanbo Wang and Mackay, {Charles R.} and Fu, {Yang Xin} and Yun Chen and Xiaohuan Guo",
note = "Funding Information: We are grateful to A. Lasorella and A. Iavarone (Columbia University, NY) for Id2-floxed mice; C. Dong and Z. Dong (Tsinghua University, Beijing) for CD45.1 and OT-I mice; B.L. Kee (the University of Chicago, IL) for ID2 and E2A plasmids; H. Peng (Institute of Biophysics CAS, Beijing) for EG7 and α-CD8; H. Qi, X. Hu, W. Zeng, M. Xu, and Y. Li (Tsinghua University, Beijing) for helpful discussions on the manuscript; and J. Wang and K. Zhu ( Tsinghua University , Beijing) for the support of statistical analysis. We are also thankful for support provided by the Animal Facility and Metabolomics Facility at Technology Center for Protein Sciences , Tsinghua University . This work was supported by the National Key R&D Program of China ( 2017YFA0103602 ), the National Natural Science Foundation of China ( 31821003 , 91642106, and 31570923 to X.G.), and Tsinghua University Initiative Scientific Research Program ( 2015Z21123 to X.G.). The Guo laboratory was also supported by the Tsinghua-Peking Center for Life Sciences , the Institute for Immunology , and the School of Medicine at Tsinghua University . Funding Information: We are grateful to A. Lasorella and A. Iavarone (Columbia University, NY) for Id2-floxed mice; C. Dong and Z. Dong (Tsinghua University, Beijing) for CD45.1 and OT-I mice; B.L. Kee (the University of Chicago, IL) for ID2 and E2A plasmids; H. Peng (Institute of Biophysics CAS, Beijing) for EG7 and ?-CD8; H. Qi, X. Hu, W. Zeng, M. Xu, and Y. Li (Tsinghua University, Beijing) for helpful discussions on the manuscript; and J. Wang and K. Zhu (Tsinghua University, Beijing) for the support of statistical analysis. We are also thankful for support provided by the Animal Facility and Metabolomics Facility at Technology Center for Protein Sciences, Tsinghua University. This work was supported by the National Key R&D Program of China (2017YFA0103602), the National Natural Science Foundation of China (31821003, 91642106, and 31570923 to X.G.), and Tsinghua University Initiative Scientific Research Program (2015Z21123 to X.G.). The Guo laboratory was also supported by the Tsinghua-Peking Center for Life Sciences, the Institute for Immunology, and the School of Medicine at Tsinghua University. X.G. is the senior and corresponding author. X.G. conceived and designed the study. X.G. Y.H. and L.F. prepared the manuscript. Y.H. and L.F. contributed equally to this work. Y.H. and L.F. performed all experiments. Y.L. W.W. X.D. M.G. J.Z. and J.H. participated in some experiments. Y.C. participated in the experiments with patients. C.R.M. and Q.W. provided critical materials. Y.-X.F. provided critical materials and helpful comments on the manuscript. The authors declare no competing interests. Publisher Copyright: {\textcopyright} 2021 Elsevier Inc.",
year = "2021",
month = may,
day = "4",
doi = "10.1016/j.cmet.2021.03.002",
language = "English (US)",
volume = "33",
pages = "988--1000.e7",
journal = "Cell Metabolism",
issn = "1550-4131",
publisher = "Cell Press",
number = "5",
}