Fig. 8: Indolent and aggressive lesions exhibit divergent tumor-immune niches.

Following introduction of the caErbB2 oncogene, transformed mammary epithelial cells form very small, early-stage lesions within mammary ducts. Over time, lesions diverge to form either indolent lesions or aggressive lesions. Indolent lesions are characterized by stereotypic, luminal-like populations, and immune infiltration into indolent lesions is limited and tend to be non-suppressed lymphoid (T cells) rather than myeloid. In contrast, aggressive lesions exhibit heterogeneous and functionally divergent tumor populations, including expanded basal-like populations as well as metaplastic and mixed-lineage tumor cells. Immune infiltration into an IL-17-active niche is heavy, primarily comprised of neutrophils or granulocytic myeloid-derived suppressor cells (G-MDSCs), while T cells are diminished in both number and activity. Indolent lesions may transition to become aggressive, evidenced by intermediate lesions that appear indolent but exhibit sub-niche expansion of basal-like cells and recruit granulocytes that are normally restricted to aggressive lesions. BM basement membrane. See also Supplementary Fig. 8.