| First Author | Beziaud L | Year | 2023 |
| Journal | Cell Stem Cell | Volume | 30 |
| Issue | 6 | Pages | 818-831.e6 |
| PubMed ID | 37267916 | Mgi Jnum | J:347552 |
| Mgi Id | MGI:7491487 | Doi | 10.1016/j.stem.2023.05.007 |
| Citation | Beziaud L, et al. (2023) IFNgamma-induced stem-like state of cancer cells as a driver of metastatic progression following immunotherapy. Cell Stem Cell 30(6):818-831.e6 |
| abstractText | Despite the remarkable success of immune checkpoint blockade (ICB) therapy, most cancer patients still do not respond. We now find that immunotherapy can induce stem-like properties in tumors. Using mouse models of breast cancer, we observe that cancer stem cells (CSCs) show not only enhanced resistance to T cell cytotoxicity, but that interferon gamma (IFNgamma) produced by activated T cells directly converts non-CSCs to CSCs. IFNgamma enhances several CSC phenotypes, such as resistance to chemo- and radiotherapy and metastasis formation. We identified the branched-chain amino acid aminotransaminase 1 (BCAT1) as a downstream mediator of IFNgamma-induced CSC plasticity. Targeting BCAT1 in vivo improved cancer vaccination and ICB therapy by preventing IFNgamma-induced metastasis formation. Breast cancer patients treated with ICB exhibited a similar increase in CSC markers expression indicating comparable responses to immune activation in humans. Collectively, we discover an unexpected, pro-tumoral role for IFNgamma that may contribute to cancer immunotherapy failure. |
