# Microbial short-chain fatty acids modulate CD8+ T cell responses and improve adoptive immunotherapy for cancer

“Microbial short-chain fatty acids modulate CD8+ T cell responses and improve adoptive immunotherapy for cancer” (2021), by Maik Luu et al. Immunology and Microbiology research paper. Original abstract below, unchanged. A free PDF is available.

- Authors: Maik Luu, Zeno Riester, Adrian Baldrich, Nicole Reichardt, Samantha Yuille, Alessandro Busetti, Matthias Klein, Anne Wempe, Hanna Leister, Hartmann Raifer et al.
- Published: July 1, 2021
- Field: Immunology and Microbiology
- DOI: https://doi.org/10.1038/s41467-021-24331-1
- Free PDF: https://www.nature.com/articles/s41467-021-24331-1.pdf

## Abstract

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.

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