RNASeq of CD206+ and CD206- Macrophages from Human Breast Tumors

Breast cancer is the leading cause of cancer-related deaths in women, demanding new treatment options. With the advent of immune checkpoint blockade, immunotherapy emerged as a treatment option. Besides lymphocytes, tumor-associated macrophages have a significant, albeit controversial, impact on tumor development. Pro-inflammatory M1 macrophages are thought to hinder, whereas anti-inflammatory M2 macrophages mainly promote tumor growth, but molecular markers to identify prognostic macrophage populations are still elusive. Based on data in murine mammary tumor models, we isolated two macrophage subsets, distinguished by the expression of CD206, which is considered as a M2 marker, from primary human breast tumors. Their transcriptome was analyzed via RNA-Seq and potential prognostic macrophage markers in tissue microarrays of patients with invasive breast cancer were validated by PhenOptics. As in the murine mammary gland, CD206+ macrophages in humans were tissue-resident and became gradually replaced by CD206- macrophages during tumor development. The presence of CD206+ macrophages correlated with a pronounced lymphocyte infiltrate and subsets of CD206+ macrophages, expressing SERPINH1 and collagen 1COL1 , or MORC4, were unexpectedly associated with improved survival of breast cancer patients. In contrast, MHCIIhi CD206- macrophages were linked with a poor survival prognosis. Our data highlight the heterogeneity of tumor-infiltrating macrophages and implicates the use of more than one phenotype marker to predict the impact of a distinct subpopulation in cancer prognosis. We identified novel macrophage markers that, independent of the M1/M2 paradigm, predict survival of patients with invasive mammary carcinoma.