| First Author | Ringel AE | Year | 2020 |
| Journal | Cell | Volume | 183 |
| Issue | 7 | Pages | 1848-1866.e26 |
| PubMed ID | 33301708 | Mgi Jnum | J:353198 |
| Mgi Id | MGI:6490155 | Doi | 10.1016/j.cell.2020.11.009 |
| Citation | Ringel AE, et al. (2020) Obesity Shapes Metabolism in the Tumor Microenvironment to Suppress Anti-Tumor Immunity. Cell 183(7):1848-1866.e26 |
| abstractText | Obesity is a major cancer risk factor, but how differences in systemic metabolism change the tumor microenvironment (TME) and impact anti-tumor immunity is not understood. Here, we demonstrate that high-fat diet (HFD)-induced obesity impairs CD8(+) T cell function in the murine TME, accelerating tumor growth. We generate a single-cell resolution atlas of cellular metabolism in the TME, detailing how it changes with diet-induced obesity. We find that tumor and CD8(+) T cells display distinct metabolic adaptations to obesity. Tumor cells increase fat uptake with HFD, whereas tumor-infiltrating CD8(+) T cells do not. These differential adaptations lead to altered fatty acid partitioning in HFD tumors, impairing CD8(+) T cell infiltration and function. Blocking metabolic reprogramming by tumor cells in obese mice improves anti-tumor immunity. Analysis of human cancers reveals similar transcriptional changes in CD8(+) T cell markers, suggesting interventions that exploit metabolism to improve cancer immunotherapy. |
