| First Author | Best SA | Year | 2022 |
| Journal | Cell Metab | Volume | 34 |
| Issue | 6 | Pages | 874-887.e6 |
| PubMed ID | 35504291 | Mgi Jnum | J:325477 |
| Mgi Id | MGI:7286138 | Doi | 10.1016/j.cmet.2022.04.003 |
| Citation | Best SA, et al. (2022) Glutaminase inhibition impairs CD8 T cell activation in STK11-/Lkb1-deficient lung cancer. Cell Metab 34(6):874-887.e6 |
| abstractText | The tumor microenvironment (TME) contains a rich source of nutrients that sustains cell growth and facilitate tumor development. Glucose and glutamine in the TME are essential for the development and activation of effector T cells that exert antitumor function. Immunotherapy unleashes T cell antitumor function, and although many solid tumors respond well, a significant proportion of patients do not benefit. In patients with KRAS-mutant lung adenocarcinoma, KEAP1 and STK11/Lkb1 co-mutations are associated with impaired response to immunotherapy. To investigate the metabolic and immune microenvironment of KRAS-mutant lung adenocarcinoma, we generated murine models that reflect the KEAP1 and STK11/Lkb1 mutational landscape in these patients. Here, we show increased glutamate abundance in the Lkb1-deficient TME associated with CD8 T cell activation in response to anti-PD1. Combination treatment with the glutaminase inhibitor CB-839 inhibited clonal expansion and activation of CD8 T cells. Thus, glutaminase inhibition negatively impacts CD8 T cells activated by anti-PD1 immunotherapy. |
