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Maik Luu, Zeno Riester, Adrian Baldrich, Nicole Reichardt, Samantha Yuille, Alessandro Busetti, Matthias Klein, Anne Wempe, Hanna Leister, Hartmann Raifer and 16 more
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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Luu, M., Riester, Z., Baldrich, A., Reichardt, N., Yuille, S., Busetti, A., Klein, M., Wempe, A., Leister, H., Raifer, H., Picard, F. S., Muhammad, K., Ohl, K., Romero, R., Fischer, F., Bauer, C. A., Huber, M., Gress, T. M., Lauth, M., … Visekruna, A. (2021). Microbial short-chain fatty acids modulate CD8+ T cell responses and improve adoptive immunotherapy for cancer. Nature Communications, 12(1), 4077. https://doi.org/10.1038/s41467-021-24331-1
Luu, Maik, et al. "Microbial short-chain fatty acids modulate CD8+ T cell responses and improve adoptive immunotherapy for cancer." Nature Communications, vol. 12, no. 1, 2021, pp. 4077, https://doi.org/10.1038/s41467-021-24331-1.
Luu, Maik, Zeno Riester, Adrian Baldrich, Nicole Reichardt, Samantha Yuille, Alessandro Busetti, Matthias Klein, et al. "Microbial short-chain fatty acids modulate CD8+ T cell responses and improve adoptive immunotherapy for cancer." Nature Communications 12, no. 1 (2021): 4077. https://doi.org/10.1038/s41467-021-24331-1.
Luu M., Riester Z., Baldrich A. [и др.] Microbial short-chain fatty acids modulate CD8+ T cell responses and improve adoptive immunotherapy for cancer // Nature Communications. — 2021. — Vol. 12, № 1. — P. 4077. — URL: https://doi.org/10.1038/s41467-021-24331-1
@article{luu2021microbial,
title = {{Microbial short-chain fatty acids modulate CD8+ T cell responses and improve adoptive immunotherapy for cancer}},
author = {Maik Luu and Zeno Riester and Adrian Baldrich and Nicole Reichardt and Samantha Yuille and Alessandro Busetti and Matthias Klein and Anne Wempe and Hanna Leister and Hartmann Raifer and Felix S.R. Picard and Khalid Muhammad and Kim Ohl and Rossana Romero and Florence Fischer and Christian Alexander Bauer and Magdalena Huber and Thomas Mathias Gress and Matthias Lauth and Sophia Danhof and Tobias Bopp and Thomas Nerreter and Imke E. Mulder and Ulrich Steinhoff and Michael Hudecek and Alexander Visekruna},
journal = {Nature Communications},
year = {2021},
volume = {12},
number = {1},
pages = {4077},
doi = {10.1038/s41467-021-24331-1},
url = {https://doi.org/10.1038/s41467-021-24331-1}
}TY - JOUR AU - Luu, Maik AU - Riester, Zeno AU - Baldrich, Adrian AU - Reichardt, Nicole AU - Yuille, Samantha AU - Busetti, Alessandro AU - Klein, Matthias AU - Wempe, Anne AU - Leister, Hanna AU - Raifer, Hartmann AU - Picard, Felix S.R. AU - Muhammad, Khalid AU - Ohl, Kim AU - Romero, Rossana AU - Fischer, Florence AU - Bauer, Christian Alexander AU - Huber, Magdalena AU - Gress, Thomas Mathias AU - Lauth, Matthias AU - Danhof, Sophia AU - Bopp, Tobias AU - Nerreter, Thomas AU - Mulder, Imke E. AU - Steinhoff, Ulrich AU - Hudecek, Michael AU - Visekruna, Alexander TI - Microbial short-chain fatty acids modulate CD8+ T cell responses and improve adoptive immunotherapy for cancer JO - Nature Communications VL - 12 IS - 1 SP - 4077 PY - 2021 DA - 2021/07/01 DO - 10.1038/s41467-021-24331-1 UR - https://doi.org/10.1038/s41467-021-24331-1 ER -
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