Cell type | Biomarker(s) | Functions in the TME | References | |
---|---|---|---|---|
T cells | CD4+ T cells | CD4 | (1) Inducing CD8+ T cell responses; (2) Secreting interferon γ (IFNγ) and tumor necrosis factor (TNF); (3) Releasing anti-inflammatory factors | [14] |
CD8+ T cells | CD8 | (1) Specific recognition of antigenic peptides-MHC class I molecular complexes; (2) Secreting IFN-γ and the protease granzyme B; (3) Killing cancer cells via perforin-mediated apoptosis and FASL-FAS-mediated cell death; (4) Noncytolytic subsets have also been identified | ||
Tregs | CD25, Foxp3 | (1) Secreting inhibitory cytokines; (2) Killing effector cells by granzymes and perforin; (3) Affecting effector cell function; (4) Reinforcing immunosuppression | [16] | |
γδ T cells | CD3, γδ | (1) Recognizing antigen in an MHC-independent way; (2) Directly recognizing cancer cells through TCR and/or natural killer cell receptors (NKRs); (3) Indirectly displaying antitumor function via influencing downstream immune responses; (4) Producing IL-17 to enhance tumorigenicity | [17] | |
B cells | CD19 | (1) Following antigen presentation; (2) Activating T cells; (3) Recognition of tumor antigens by BCRs and direct killing of tumor cells; (4) Generation of pro-inflammatory factors like IL-1β (5) Inhibiting anti-cancer immunity through promotion of immune tolerance and direct suppression of T cells | [19] | |
Macrophages | M1 | CD86, CD64, MARCO | (1) Direct cytotoxicity; (2) Tumor cell elimination through ADCC | |
M2 | CD206, CD163, ARG1 | (1) Immunosuppression; (2) Releasing chemokines such as VEGFA, PDGF, MMPs, HIF, IL-10, COX2, and adrenomedullin to facilitate angiogenesis and lymphangiogenesis; (3) Promoting metastasis; (4) supporting drug resistance | ||
Dendritic cells (DCs) | CD11c, HLA-DR | (1) Presenting antigen; (2) Inducing and maintaining CD8+ T cell responses | ||
Mast cells | CD32, CD33, CD117 | (1) Promoting angiogenesis via secreting factors like IL-8, NGF, TGF-β VEGF-A, and VEGF-B; (2) Releasing MMPs to support tumor invasion; (3) Eliminating tumor cells through secreting IL-1, IL-4, IL-6, and TNF-α; (4) Enhancing tumor expansion via secreting FGF-2, NGF, PDGF, VEGF, IL-8, and IL-10 | ||
NK cells | CD56, NKp46, CD94 | (1) Tumor cytotoxic activity; (2) Killing cancer cells via the ‘missing-self’ mechanism; (3) Secreting cytokines like IFN-γ and TNF-α | ||
Monocytes | CD14 | (1) Differentiating into TAMs, tumor-associated DCs (TADCs), and MDSCs; (2) Tumor cytotoxicity; (3) Activating APCs; (4) Potentiating angiogenesis and reshaping ECM (5) Immunosuppression | ||
Neutrophils | CD11b, CD16 | (1) Directly killing cancer cells and trogoptosis; (2) Altering TME through improving T lymphocyte response and influencing macrophages; (3) releasing ROS and PGE2; (4) Immunosuppression; (5) Promoting cancer angiogenesis | [24] | |
Eosinophils | CD125, Siglec-8+ | (1) Tumor cell toxicity; (2) Vessel normalization; (3) Secreting various soluble factors such as IL-10, IL-12 and cytotoxic proteins, such as MBP and ECP; (4) favoring tumor progression via remodeling ECM, inducing macrophage polarization, and suppressing immune response | [25] | |
Basophils | CD22, CD123 | (1) Releasing proangiogenic factors like VEGF-A, VEGF-B, ANGPT1, and HGF; (2) Secreting granzyme B, TNF-α, and histamine | ||
Mesenchymal stromal cells (MSCs) | CD105, CD73, CD90 | (1) Promoting tumor growth and progression via secreting cytokines and chemokines like VEGF, TGF-β1, IL-6 and IL-8; (2) Tumor toxicity and TLR expression; (3) Exosome releasing | ||
Myeloid-derived suppressor cells (MDSCs) | CD11b, Gr 1, Ly6G, Ly6C | (1) Suppressing T-cell through the high expression of ARG1, iNOS, and ROS and depletion of required amino acids; (2) Inhibiting NK cells, DCs, and B cells; (3) Promoting vascularization and pre-metastatic niche formation | ||
Cancer-associated fibroblasts (CAFs) | FAP, α-SMA | (1) Promoting tumor growth, angiogenesis, metastasis, and drug resistance; (2) Remodeling ECM; (3) Suppressing immunity; (4) Cancer-restraining function | ||
Pericytes | PDGFR-β, αSMA, CD146, NG2 | (1) Modulating immunosuppressive TME; (2) Forming the pre-metastatic niche; (3) Participating in EMT | ||
Adipocytes | ASC-1 | (1) Secreting pro-inflammatory cytokines, adiponectin, and autotaxin (ATX); (2) Altering cancer cell metabolism |