Abstract
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.
Highlights
Tumor associated macrophages (TAMs) play a critical role in biology of various cancers, including breast cancer
Despite previous reports that high infiltration of M1-like macrophage was associated with better survival outcome, we found that transcriptomically defined “M1” high tumors were not associated with favorable survival outcome with regards to overall survival (OS), disease specific survival (DSS), and disease-free survival (DFS)
We found that high “M1” tumors enriched the gene sets related to cell proliferation and cell cycle with Gene set enrichment analysis (GSEA)
Summary
Tumor associated macrophages (TAMs) play a critical role in biology of various cancers, including breast cancer. Infiltration by M1 was reported to be associated with aggressive clinical features such as high Nottingham pathological grade and increased cell proliferation marker, Ki-6715 The balance between these two polarized macrophages is important because previous studies demonstrated that TAMs are predominantly M2-like macrophages and they are associated with cancer progression[16,17,18]. There is no doubt of usefulness of these technologies in basic research setting, their utility in large sample size of clinical patients can be challenging given the access to samples, costs and labor involved To overcome this difficulty, we defined TAMs as “M1” and “M2” macrophages following the transcriptomic marker defined in the computational algorithm, xCell, developed by Aran et al.[27]. We analyzed the transcriptome of large breast cancer patient cohorts including The Cancer Genome Atlas (TCGA) and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC)
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