| First Author | Anstee JE | Year | 2023 |
| Journal | Dev Cell | Volume | 58 |
| Issue | 17 | Pages | 1548-1561.e10 |
| PubMed ID | 37442140 | Mgi Jnum | J:340309 |
| Mgi Id | MGI:7528589 | Doi | 10.1016/j.devcel.2023.06.006 |
| Citation | Anstee JE, et al. (2023) LYVE-1(+) macrophages form a collaborative CCR5-dependent perivascular niche that influences chemotherapy responses in murine breast cancer. Dev Cell 58(17):1548-1561.e10 |
| abstractText | Tumor-associated macrophages (TAMs) are a heterogeneous population of cells that facilitate cancer progression. However, our knowledge of the niches of individual TAM subsets and their development and function remain incomplete. Here, we describe a population of lymphatic vessel endothelial hyaluronan receptor-1 (LYVE-1)-expressing TAMs, which form coordinated multi-cellular "nest" structures that are heterogeneously distributed proximal to vasculature in tumors of a spontaneous murine model of breast cancer. We demonstrate that LYVE-1(+) TAMs develop in response to IL-6, which induces their expression of the immune-suppressive enzyme heme oxygenase-1 and promotes a CCR5-dependent signaling axis, which guides their nest formation. Blocking the development of LYVE-1(+) TAMs or their nest structures, using gene-targeted mice, results in an increase in CD8(+) T cell recruitment to the tumor and enhanced response to chemotherapy. This study highlights an unappreciated collaboration of a TAM subset to form a coordinated niche linked to immune exclusion and resistance to anti-cancer therapy. |
