Home Publications Research Grants Inventions & Patents Awards Additional Research Activities Faculties & Institutions Research Areas

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

Luu M, Riester Z, Baldrich A, Reichardt N, Yuille S, Busetti A, Klein M, Wempe A, Leister H, Raifer H, Picard F, Muhammad K, Ohl K, Romero R, Fischer F, Bauer CA, Huber M, Gress TM, Lauth M, Danhof S, Bopp T, Nerreter T, Mulder IE, Steinhoff U, Hudecek M, Visekruna A (2021)

---

Publication Type: Journal article

Publication year: 2021

Journal

Book Volume: 12

Article Number: 4077

Journal Issue: 1

DOI: 10.1038/s41467-021-24331-1

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.

Involved external institutions

How to cite

APA:

Luu, M., Riester, Z., Baldrich, A., Reichardt, N., Yuille, S., Busetti, A.,... Visekruna, A. (2021). Microbial short-chain fatty acids modulate CD8+ T cell responses and improve adoptive immunotherapy for cancer. Nature Communications, 12(1). https://doi.org/10.1038/s41467-021-24331-1

MLA:

Luu, Maik, et al. "Microbial short-chain fatty acids modulate CD8+ T cell responses and improve adoptive immunotherapy for cancer." Nature Communications 12.1 (2021).

BibTeX: Download