1区 · 综合性期刊
ArticleOA
作者: Gress, Thomas M ; Visekruna, Alexander ; Romero, Rossana ; Baldrich, Adrian ; Steinhoff, Ulrich ; Huber, Magdalena ; Bauer, Christian A ; Bopp, Tobias ; Muhammad, Khalid ; Nerreter, Thomas ; Picard, Felix ; Hudecek, Michael ; Mulder, Imke E ; Luu, Maik ; Danhof, Sophia ; Raifer, Hartmann ; Lauth, Matthias ; Wempe, Anne ; Klein, Matthias ; Leister, Hanna ; Yuille, Samantha ; Riester, Zeno ; Reichardt, Nicole ; Busetti, Alessandro ; Ohl, Kim ; Fischer, Florence
AbstractEmerging 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.
