“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.

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

Maik Luu, Zeno Riester, Adrian Baldrich et al. · July 1, 2021 · Immunology and Microbiology

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.

Free PDF DOI: 10.1038/s41467-021-24331-1