Glutamine blockade induces divergent metabolic programs to overcome tumor immune evasion
Menée à l'aide de modèles murins de cancer du côlon, de lymphome ou de mélanome, cette étude met en évidence l'intérêt de bloquer le métabolisme de la glutamine pour lever l'échappement immunitaire des cellules cancéreuses
The metabolic characteristics of tumors present significant hurdles to immune cell function and cancer immunotherapy. Using a novel glutamine antagonist, we metabolically dismantled the immunosuppressive microenvironment of tumors. We demonstrate that glutamine blockade in tumor-bearing mice suppresses oxidative and glycolytic metabolism of cancer cells, leading to decreased hypoxia, acidosis, and nutrient depletion. In contrast, effector T cells responded to glutamine antagonism by markedly upregulating oxidative metabolism and adopting a long-lived, highly-activated phenotype. These divergent changes in cellular metabolism and programming form the basis for potent anti-tumor responses. Glutamine antagonism therefore exposes a previously undefined difference in metabolic plasticity between cancer cells and effector T cells that can be exploited as a “metabolic checkpoint” for tumor immunotherapy.