Skip to main content
. 2022 Sep 16;66(4):319–331. doi: 10.1042/EBC20220016

Figure 4. Simplified view of immune-landscape plasticity.

Figure 4

(A) Proinflammatory tumor microenvironment (TME). An inflammatory TME is generated by immune-stimulating cancer-associated fibroblasts (CAFs), leukocyte-attracting endothelial cells (ECs) and proinflammatory immune cells, such as antigen-presenting dendritic cells (DCs), M1-like tumor-associated macrophages (M1-TAMs), CD4+ helper T (Th1-like) cells, CD8+ cytotoxic T cells, natural killer (NK) cells and B cells. Immune surveillance is preserved in an inflammatory TME with active immune cells, whereas immune tolerance is elicited in an inflammatory TME with exhausted immune cells (featuring a hot immune environment with strong immune evasion); CCL2, C-C motif chemokine ligand 2; CSC, cancer stem cell; IFNγ, interferon-γ also known as IFNG; IL1β, interleukin-1β; TNF, tumor necrosis factor. (B) Immunosuppressive TME. A noninflammatory TME is established by angiogenic ECs, CAFs remodeling extracellular matrix (ECM), M2-TAMs, myeloid-derived suppressor cells (MDSCs) and regulatory T (Treg) cells. Transforming growth factor-β (TGFβ) gives rise to ECM-remodeling CAFs, M2-TAMs, monocytic MDSCs and Treg cells. Monocytic MDSCs produce IL10, TGFβ and vascular endothelial growth factor (VEGF). VEGF-induced tumor angiogenesis generates a hypoxic and acidic TME. Immune tolerance is elicited in a noninflammatory TME (featuring a cold immune environment with strong immune evasion). (C) WNT- and TGFβ-dependent immune regulation. (Left) Canonical WNT signaling activation in CD8+ T and Treg cells enhances antitumor immunity through production of proinflammatory cytokines, such as IFNγ and TNF. (Middle) Canonical WNT signaling activation in tumor cells promotes cold immune evasion through up-regulation of CCL28, CD274 (PD-L1, PD-1 ligand 1) and WISP1. (Right) TGFβ, noncanonical WNT and YAP signaling network establishes immunosuppressive TME through potentiation of the TGFβ signaling loop. Canonical WNT signaling promotes immune surveillance as well as immune tolerance in a context-dependent manner, whereas TGFβ signaling generates cold immune evasion.