Microbial short-chain fatty acids modulate CD8+ T cell responses and improve adoptive immunotherapy for cancer
By Maik Luu, Zeno Riester, Adrian Baldrich, Nicole Reichardt, S. Yuille, A. Busetti, M. Klein, Anne Wempe, Hanna Leister, H. Raifer and 16 more. Nature Communications, 2021
650 citations recorded by the source corpus.
Emerging data demonstrate that the activity of immune cells can be modulated by microbial molecules. Here, we show that the short-chain fatty acids (SCFAs) pentanoate and butyrate enhance the anti-tumor activity of cytotoxic T lymphocytes (CTLs) and chimeric antigen receptor (CAR) T cells through metabolic and epigenetic reprograming. We show that in vitro treatment of CTLs and CAR T cells with pentanoate and butyrate increases the function of mTOR as a central cellular metabolic sensor, and inhibits class I histone deacetylase activity. This reprogramming results in elevated production of effector molecules such as CD25, IFN-γ and TNF-α, and significantly enhances the anti-tumor activity of antigen-specific CTLs and ROR1-targeting CAR T cells in syngeneic murine melanoma and pancreatic cancer models. Our data shed light onto microbial molecules that may be used for enhancing cellular anti-tumor immunity. Collectively, we identify pentanoate and butyrate as two SCFAs with therapeutic utility in the context of cellular cancer immunotherapy. The activity of immune cells can be regulated by the microbiome. Here, the authors show that the fatty acids pentanoate and butyrate—normally released by the microbiome—increase the anti-tumour activity of cytotoxic T lymphocytes and chimeric antigen receptor T cells through metabolic and epigenetic reprogramming.
Subfields: Immunology, Molecular Biology, Oncology
View Paper: https://www.semanticscholar.org/paper/c6889c2adb2d2b120c0c7693bb5521bd22fb69a3
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Citations in the corpus
- Short-chain fatty acids: linking diet, the microbiome and immunity (2024, positive): “The immunomodulatory properties of SCFAs, particularly butyrate, might apply to tumour-specific cytotoxic T lymphocytes and CAR T cells 96 .”