Fig. 3

The proposed mechanisms of tumor microenvironment in metastatic TNBC. DC,dendritic cells, MHC major histocompatibility complex, TGF-β transforming growth factor-beta, Treg T-regulatory cells, M2 macrophage type 2, Th T-helper cell, TCR T-cell receptor TRAIL, tumor necrosis factor-related apoptosis-inducing ligand. The antitumor immune system works directly against cancer cells, whereas the protumor immune system works indirectly by suppressing the antitumor immune system. The activities of CD4 and CD8 immune cells have a direct impact on tumor cells. The activation of DC is initiated by CD4, which subsequently triggers the activation of CD8. CD4 cells induce apoptosis in cancer cells by secreting IFNγ, TNFα, and via p-MHC II, whereas CD8 cells induce apoptosis by producing granzyme, perforin, and activating the FasL/TRAIL pathway. Protumor immune cells of CD163 and FOXP3 exert their effects indirectly by inhibiting the antitumor immune cells mediated by the PD-L1/PD-1, CTLA/B7, FasL/TRAIL pathway, and IL-10 secretion. The CD163 secretes CCL2, CCL5, and CCL20 which attract the FOXP3 cells in the TME. It also secretes IL-10 and TGF-β which suppress the TCR expression. Adenosine induces the apoptosis of CD8 and suppresses the TCR expression. Created with biorender.com. Figure courtesy of Jeffry Beta Tenggara. Permission to reuse the figure in any form must be obtained directly from Jeffry Beta Tenggara.