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. 2021 Jun 18;22(12):6526. doi: 10.3390/ijms22126526

Figure 2.

Figure 2

Multifaceted Roles of TAMs in TME. TAMS facilitate tumor growth by activating various signaling pathways including, signal transducer, and activator of transcription 3 (STAT3). The presence of M-CSF, IL-10, MMP9, and hypoxia assist TAMs in facilitating tumor growth. With tumor advancement, TAMs can either recruit immunosuppressive leukocytes or inhibit cytotoxic functions of immune cells in order to activate immunosuppression. Inhibition of cytotoxic T cell activities and recruitment causes drug resistance. Activation of the IL-10-STAT3-BCL2 pathway or cytokines and growth factors such as CCL18, basic fibroblast growth factor (bFGF), and VEGF in the TME further accelerates this TAM-mediated drug resistance. TAMs promote angiogenesis in the presence of cytokines such as MMPs and growth factors such as VEGF, PDGF, and TGFβ. TAM-mediated activation of CCL8, WNT7B, PDPN, and TIE2 expression can also lead to angiogenesis in the TME. Once angiogenesis starts, tumor and TAMs together initiate extracellular matrix (ECM) degradation resulting in tumor migration and metastasis.