. 2020 Jul 27;9(8):1785. doi: 10.3390/cells9081785

Table 1.

Role of tumor-associated macrophages and myeloid-derived suppressor cells in breast cancer.

Cell Types	Roles	References
TAM-Immune mechanism	Suppress CD8⁺T-cell activation by IL-10 Repress effector T-cells by reduced L-arginine level by Arg1 Inhibit T-cell response in murine mammary tumor by Arg1 and iNOS Tumor immune invasion in mouse breast tumor by decreased IL-12 and iNOS *Decreased antigen presentation from reduced MHC class II expression	[61,62] [164] [65] [66,67] [68]
TAM-Nonimmune mechanism	Promote angiogenesis by VEGF overexpression Correlation between TAM infiltration and increased angiogenesis in human breast cancer Secret increased amounts of angiogenesis mediator transcripts in the late stage mammary cancer Promote breast cancer progression by ECM remodeling via uPAR expression in human breast cancer Produce type I collagen in mouse breast tumor Activate cancer stem cell by IL-6 Enhance tumor sphere formation in co-culture of ER-positive breast cancer cell line and M2 macrophages Interact with breast CSC and enhanced tumor formation and maintenance of CSC Contribute mammary tumor intravasation by interaction between EGF from TAM and CSF1 from breast cancer cells Promote breast cancer cell intravasation by integrin clustering via CCL18 Involve lung metastasis of breast cancer by CD11b-positive macrophage recruitment by CCL2 Enhance metastasis by CXCL1 in breast cancer cells	[74] [75,76] [25] [77] [78] [79] [80] [82] [86,87] [88] [92] [93]
TAM-Metabolic interaction	Increase breast cancer cell proliferation by ARG1-mediated polyamine production Increase breast cancer cell proliferation by increased secretion of lipocalin *Enhance breast cancer growth through heme oxygenase-1 in mouse model	[96] [165] [107]
TAM-Treatment resistance induction	Increased treatment response of docetaxel in depletion of M2 TAM and expansion of M1 TAM in breast cancer Induce treatment resistance in breast cancer though IL-10/STAT3/Bcl-2 signaling pathway in TAM [111] and secretion of chemoprotective molecules like cathepsin B and S in TAM *Result in resistance to antiangiogenesis agent by fibroblast growth factor, chemokine CCL18, thymidine phosphorylase, urokinase-type plasminogen activator (uPA), adrenomedullin (ADM), and semaphorin 4D (Sema4D) in TAM	[110] [113] [114]
MDSC-Immune mechanism	*Inhibit CD8⁺T-cells through granulocytic MDSC activated by IL-17 in breast cancer	[137]
MDSC-Nonimmune mechanism	Inhibit PTEN and activate AKT pathway by activated miRNA-494 in MDSCs in breast cancer cell Enhance breast cancer stemness through Notch and STAT3 activation by NO release Promote breast cancer invasiveness and metastasis through STAT3 activation by IL-6 and IL6Rα and by increased AKT pathway and MMP expression Induce EMT, tumor cell migration, and invasion through PI3K-AKT-mTOR pathway activation by MDSC in breast cancer cells Promote osteolytic bone metastasis by acting as osteoclast progenitors Promote metastasis through MMP and TGF-β1 by Gr-1⁺CD11b⁺ myeloid cell recruitment Involve in extravasation, seeding, and tumor cell growth by differentiating monocytic MDSC into metastasis-associated macrophages Promote EMT, tumor cell proliferation, and metastasis by secreting versican in CD11b⁺Ly6C^high monocytic MDSCs and by secreting TGF-β, VEGF, and IL-10 *Enhance cancer stemness in TNBC by MMP9 and chitinase 3-like 1 secretion	[52] [143] [46,144] [145] [49,146,147] [124] [148] [149,150] [151]