TY  - JOUR
A1  - Luu, Maik
A1  - Riester, Zeno
A1  - Baldrich, Adrian
A1  - Reichardt, Nicole
A1  - Yuille, Samantha
A1  - Busetti, Alessandro
A1  - Klein, Matthias
A1  - Wempe, Anne
A1  - Leister, Hanna
A1  - Raifer, Hartmann
A1  - Picard, Felix
A1  - Muhammad, Khalid
A1  - Ohl, Kim
A1  - Romero, Rossana
A1  - Fischer, Florence
A1  - Bauer, Christian A.
A1  - Huber, Magdalena
A1  - Gress, Thomas M.
A1  - Lauth, Matthias
A1  - Danhof, Sophia
A1  - Bopp, Tobias
A1  - Nerreter, Thomas
A1  - Mulder, Imke E.
A1  - Steinhoff, Ulrich
A1  - Hudecek, Michael
A1  - Visekruna, Alexander
T1  - Microbial short-chain fatty acids modulate CD8+ T cell responses and improve adoptive immunotherapy for cancer
JF  - Nature Communications
N2  - 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.
KW  - tumour immunology
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-309332
VL  - 12
ER  -