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. 2022 Nov 7;14(21):5460. doi: 10.3390/cancers14215460

Figure 1.

Figure 1

TAMs in the breast cancer TME. 1. The effect of TAMs on T cells: 1.a. TAMs can suppress T-cell proliferation via the programmed death-ligand 1 (PDL-1) [42]. 1.b. TGF-beta affects T-cell function by upregulation of PDL-1 on TAMs [42]. 1.c. Tregs are induced by IL-10, TGF-B, and PDGF-2, thus suppressing T cells [45]. 1.d. Treg recruitment happens through CCL7/8/22 [45]. 1.e. Increased activity of arginase enzyme and iNOS result in the increased level of NO and RNOS (ONOO−) leading to nitrosylation and thus impairing T-cell self-stimulation by IL-2 in addition to nitration of TCR signaling complex altering T-cell function [23]. 2. The effect of TAMs on NK cells: 2.a. The inhibitory effect of TAMs can be due to the expression of PDL-1 (which is highly expressed on TAMs) or 2.b. it can be due to TGF-B secretion [42]. 2.c. TAMs also suppress NK IFN-Y production [42]. 3. TAMs induce angiogenesis by releasing VEGF, PDGF, and IL-8 [23]. 4. Interaction between TAMs and cancer cells: 4.a. It was observed that VCAM1+ tumor cells have increased survival in a leukocyte-rich environment due to the adhesion of leukocyte receptors on BC cells (VCAM1) to TAM α 4 integrin [21]. 4.b. TGF-B was shown to upregulate PDL-1 on cancer cells, thus inducing an inhibitory effect on immune cells [23]. 4.c. There is a paracrine loop between cancer cells and TAMs. TAMs secrete epidermal growth factor (EGF) that binds to EGFRs on the cancer cells [21]. 4.d. TAMs express M-CSFR, which is a monocyte colony-stimulating factor receptor also known as colony-stimulating factor 1 receptor (CSF-1R or cFMS). The M-CSFR binds to the M-CSF (CSF-1) that is produced by cancer cells [41]. The binding of cancer cells with TAMs allows the co-migration of two different cell types, thus enhancing invasion, motility, and intravasation [21]. 5. CD163 and C206 are considered the commonly used self-markers for TAMs. 6. MCP-1 is a monocyte recruiter that is produced by TAMs; monocytes respond to TME and differentiate into TAMs [46]. 7.a. TAMs coordinate in the extracellular proteolysis through the secretion of tissue-remodeling cysteine cathepsin proteases that contribute to ECM and collagen degradation [47]. 7.b. Moreover, MMPs contribute to collagen degradation. Types I, III, IV, and VI are the major collagens that play an important role in tumors [47]. Myeloid cells remodel ECM by degrading the collagen through matrix metalloproteinases (MMPs) [34].