Journal
ONCOIMMUNOLOGY
Volume 8, Issue 10, Pages -Publisher
TAYLOR & FRANCIS INC
DOI: 10.1080/2162402X.2019.1616153
Keywords
Autophagy; aging; hydroxycitrate; immune checkpoints; immunometabolism; longevity; methionine
Categories
Funding
- Ligue contre le Cancer
- Agence National de la Recherche (ANR) -Projets blancs
- ANR under the frame of E-Rare-2, the ERA-Net for Research on Rare Diseases
- Association pour la recherche sur le cancer (ARC)
- Canceropole Ile-de-France
- Chancelerie des universites de Paris (Legs Poix), Fondation pour la Recherche Medicale (FRM)
- European Research Area Network on Cardiovascular Diseases (ERA-CVD, MINOTAUR)
- Gustave Roussy Odyssea, the European Union Horizon 2020 Project Oncobiome
- Fondation Carrefour
- High-end Foreign Expert Program in China, Institut National du Cancer (INCa) [GDW20171100085, GDW20181100051]
- Inserm (HTE)
- Institut Universitaire de France
- LeDucq Foundation
- LabEx Immuno-Oncology
- RHU Torino Lumiere
- Seerave Foundation
- SIRIC Stratified Oncology Cell DNA Repair and Tumor Immune Elimination (SOCRATE)
- SIRIC Cancer Research and Personalized Medicine (CARPEM)
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Recent findings have shed new light on the mechanisms through which tumor-infiltrating lymphocytes (TILs) maintain their cytotoxic potential in the context of checkpoint blockade or adoptive transfer therapies. As a consequence of the ionic unbalance occurring in the tumor microenvironment, TILs enter an adaptive caloric-restricted state, characterized by a decline in nucleocytosolic acetyl CoA levels and induction of autophagy. These events dictate an epigenetic program that drives the acquisition of a stem-cell-like phenotype and ultimately improves antitumor function. These findings open the way to novel anticancer therapies based on the induction of autophagy by pharmacological caloric restriction mimetics.
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