Targeting Glutamine Metabolism to Enhance Immunoprevention of EGFR-Driven Lung Cancer.

ABSTRACT: Lung cancer is the leading cause of cancer death worldwide. Vaccination against EGFR can be one of the venues to prevent lung cancer. Blocking glutamine metabolism has been shown to improve anticancer immunity. Here, the authors report that JHU083, an orally active glutamine antagonist prodrug designed to be preferentially activated in the tumor microenvironment, has potent anticancer effects on EGFR-driven mouse lung tumorigenesis. Lung tumor development is significantly suppressed when treatment with JHU083 is combined with an EGFR peptide vaccine (EVax) than either single treatment. Flow cytometry and single-cell RNA sequencing of the lung tumors reveal that JHU083 increases CD8⁺ T cell and CD4⁺ Th1 cell infiltration, while EVax elicits robust Th1 cell-mediated imm

SUBMITTER: Huang M 

PROVIDER: S-EPMC9475521 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature