Figure 3.

Mechanisms of three distinct tumor phenotypes. Three different phenotypes are associated with specific biological mechanisms. Tumors with the immune-desert phenotype (yellow) may lack T-cell priming due to the absence of tumor antigens, defective antigen processing and presentation machinery, or impaired DC-T-cell interactions. Tumors with the immune-excluded phenotype (blue) may exhibit activation of oncogenic pathways, aberrant chemokines, aberrant vasculature and hypoxia, or an immunosuppressive tumor microenvironment (e.g., stromal barriers). Tumors with the immune-inflamed phenotype (red) can be infiltrated by many immune cells, but these immune cells are suppressed due to checkpoint activation. ADO: adenosine; ATP, adenosine triphosphate; B2M: beta-2-microglobulin; BATF3: basic leucine zipper ATF-like transcription factor 3; CAFs: cancer-associated fibroblasts; CRT, calreticulin; CTLA4, cytotoxic T lymphocyte-associated antigen-4; CXCL: CXC-chemokine ligand; DNMT: DNA methyltransferase; ECM: extracellular matrix; ETBR: endothelin B receptor; EZH2: enhancer of zeste homolog 2; FLT3L: Fms-like tyrosine kinase 3 ligand; GM-CSF: granulocyte-macrophage colony-stimulating factor; HDAC: histone deacetylase; HEV: high endothelial venule; HMGB1: high mobility family protein B1; ICAM: intercellular adhesion molecule; IDO: Indoleamine 2,3-dioxygenase; IFN: interferon; IL: interleukin; MDSC: myeloid-derived suppressor cell; MHC: major histocompatibility complex; PD-1, programmed cell death protein 1; PD-L1, PD-1 ligand; STC1: stanniocalcin 1; TAM: tumor-associated macrophage; TAP: transporter associated with antigen processing; TGFβ: transforming growth factor-β; TIM3, T cell immunoglobulin and mucin domain-containing 3; TLR: Toll‑like receptor; TLS: tertiary lymphoid structure; TME: tumor microenvironment; Treg: T-regulatory cell; VCAM: vascular cell adhesion molecule; VEGF: vascular endothelial growth factor.