Breast cancer is a heterogeneous disease, and disparate immune responses in breast cancer regulate tumour progression and responses to chemotherapy. These immune responses are, in part, orchestrated by diverse macrophage subtypes that are shaped by the local environment. Although the pro-tumorigenic functions of macrophages are well-annotated across human cancers, the precise molecular and cellular mechanisms that regulate macrophage heterogeneity are not well understood. In a recent preprint (not peer-reviewed), Ben-Chetrit et al. investigate the regulation of macrophage heterogeneity in solid breast cancer tumours.

Using an organotypic tumour microenvironment (oTME) system derived from the MMTV-PyMT transgenic mouse model of mammary cancer, the authors show that F4/80hiSCA1+ self-renewing macrophages colocalize with tumour stroma, independently of levels of the growth factor CSF1. They also show that macrophage self-renewal requires contact with oTME cells and that co-culture with cancer-associated fibroblasts (CAFs), but not steady-state fibroblasts, is required for proliferation of stroma-associated macrophages (SAMs). Conversely, macrophages that colocalize with tumour epithelial cells do not self-renew. Together, these experiments suggest that CAFs maintain self-renewing SAMs in a contact-dependent manner.