M1 Macrophage and M1/M2 ratio defined by transcriptomic signatures resemble only part of their conventional clinical characteristics in breast cancer

Tumor associated macrophages (TAMs) play a critical role in biology of various cancers, including breast cancer. In the current study, we defined M1 macrophage and M1/M2 ratio by transcriptomic signatures using xCell. We investigated the association between high level of M1 macrophage or M1/M2 ratio and the tumor immune microenvironment by analyzing the transcriptome of publicly available cohorts, TCGA and METABRIC. We found that M1 high tumors were not associated with prolonged survival compared with M1 low tumors, or with the response to neoadjuvant chemotherapy. M1 high tumors were associated with clinically aggressive features and M1 high tumors enriched the cell proliferation and cell cycle related gene sets in GSEA. At the same time, M1 high tumors were associated with high immune activity and favorable tumor immune microenvironment, as well as high expression of immune check point molecules. Strikingly, all these results were mirrored in M1/M2 ratio high tumors. In conclusion, transcriptomically defined M1 or M1/M2 high tumors were associated with aggressive cancer biology and favorable tumor immune microenvironment but not with survival benefit, which resembled only part of their conventional clinical characteristics.