| First Author | Clark NM | Year | 2020 |
| Journal | Cell Rep | Volume | 33 |
| Issue | 10 | Pages | 108482 |
| PubMed ID | 33296659 | Mgi Jnum | J:301982 |
| Mgi Id | MGI:6489190 | Doi | 10.1016/j.celrep.2020.108482 |
| Citation | Clark NM, et al. (2020) Regulatory T Cells Support Breast Cancer Progression by Opposing IFN-gamma-Dependent Functional Reprogramming of Myeloid Cells. Cell Rep 33(10):108482 |
| abstractText | Regulatory T (Treg) cell infiltration of solid tumors often correlates with poor prognosis, but their tumor-suppressive function lacks mechanistic understanding. Through a combination of transgenic mice, cell fate mapping, adoptive transfer, and co-injection strategies, we demonstrate that Treg cell ablation-dependent anti-tumor effects in murine breast cancer require intratumoral recruitment of CCR2(+) inflammatory monocytes, which primarily differentiate into tumor-associated macrophages (TAMs), and lead to reprogramming of their function in an IFN-gamma-dependent manner. Furthermore, transcriptomic signatures from murine TAMs in Treg cell-ablated conditions correlate with increased overall survival in human breast cancer. Our studies highlight the strong myeloid dependency of breast cancer and provide the basis for the development of therapeutic strategies based on manipulation of the IFN-gamma signaling pathway in monocytes. |
