Macrophage subtypes inhibit breast cancer proliferation in culture.

Abstract

Macrophages are a highly plastic cell type that adopt distinct subtypes and functional states depending on environmental cues. These functional states can vary widely, with distinct macrophages capable of displaying opposing functions. We sought to understand how macrophage subtypes that exist on two ends of a spectrum influence the function of other cells. We used a coculture system with primary human macrophages to probe the effects of macrophage subtypes on breast cancer cell proliferation. Our studies revealed a surprising phenotype in which both macrophage subtypes inhibited cancer cell proliferation compared with cancer cells alone. Of particular interest, using two different proliferation assays with two different breast cancer cell lines, we showed that differentiating macrophages into a "protumor" subtype inhibited breast cancer cell proliferation. These findings are inconsistent with the prevailing interpretation that "protumor" macrophages promote cancer cell proliferation and suggest a re-evaluation of how these interpretations are made.