Table 1.
Composition of cells in TME with their functions and primary secreted factors.
| Cell Type | General Function | Role in TME | Factors Through Which They Exhibit Anti-Tumor Effects | Factors Through Which They Exhibit Pro-Tumor Effects |
|---|---|---|---|---|
| Macrophages (MP) [11,12,13,14] | Phagocytosis of defective cells, pro-inflammatory effect, or immunomodulation | M1: Anticancer. M2: Pro-cancerous; inhibition of the inflammatory process |
IFN-γ, IL-12, GM-CSF | IL-1, IL-6, IL-1β, IL-10, TNF-α, TGF-β, EGF, VEGF, FGF, MMP, CCL2, CCL5, CCL3, CCL8, CCL22 |
| Dendritic cells (DC) [15,16] | Antigen presentation, effect on the activity of helper and regulatory lymphocytes | Disturbed antigen presentation, maturation, and infiltration of the tumor | Il-6, Il-8, Il-12, Il-15, TNF-α | IDO |
| (Nφ) Neutrophils [17,18,19] |
Phagocytosis, ADCC, Stimulation of lymphocytes and NK cells | N1 (anti-tumor): phagocytosis, stimulation of apoptosis, activation of CD8+ T cells N2 (pro-tumor): angiogenesis, stimulation of inflammatory processes in the tumor, T cell suppression |
TNF-α, IFN-γ, Il-12, CCL3, CXCL9, CXCL10, ROS, MMP9 | TGF-β, MPO, MMP9, HGF, VEGF, oncostatin M, ROS, RNS, MMPs, NE, IL-1β, elastase, PGE2, transferrin |
| Cytotoxic T lymphocytes (CTL) [20,21] | Cytotoxic effect, stimulation of other immune cells | Disruption of cytotoxic effects by binding to PD-L1 | Perforins, granzymes, IL-2, TNF-α, IFN-γ | none |
| T helper lymphocytes (Th cells) [22,23] | Stimulate by Th1 of dendritic cells and NK cells | Th1—inhibition of Treg, Th2 and M2 by Il-10, Il-4, TGF-β Th2—stimulation of M2 and inhibition of Th1 |
TNF-α, Il-12, Il-17, Il-18, Il-21, Il-27 | IL-17A, IL-17F, IL-21 and IL-22 |
| T regulatory lymphocytes (Treg) [24,25] | Protection against autoimmune reactions | Immunosuppression, facilitating of immune tolerance | IL-10, TGF-β, PGE2, IL-35 | TGF-β, IL-2, IL-10, IL-35 |
| B lymphocytes (BC—B cell) [26,27,28] | Antibody production, complement activation, antigen presentation | Stimulation of Treg, enhanced angiogenesis, inhibition of Tc, production of anti-inflammatory factors | Il-2, Il-6, IFN-α, IFN-γ, granzyme B, lymphotoxin | Il-8, Il-10, TGF-β, Il-1β, Il-35, lymphotoxin |
| Natural Killer cells (NK) [29,30] | Cytotoxic effects, stimulation of T lymphocytes and dendritic cells | Inhibition of NK activity by disrupting their activation | IL-2, 6, 12, 15, TNF-α, IFN-γ, GM-CSF, CCL3-CCL5 | none |
| Cancer-associated fibroblasts (CAF) [31,32,33] |
none | Pro-inflammatory effects, secretion of growth factors, angiogenesis | none | CXCL1,2,3,12, CCL2,5,17, IL-6, Il-8, Il-11, GM-CSF, TGF-β, MMPs, FGF exosomes, VEGF-A, PGE2, PDGF-C, IGF-1, HGF, CTGF |
| Cancer-associated adipocytes (CAA) [34,35,36] | none | Secretion of adipokines | none | Leptin, HGF, Il-1β, Il-6, Il-8, G-CSF, CCL2, CCL5 |
| Myeloid-derived suppressor cells (MDSC) [37,38] | none | Suppression of the immune response, promotion of angiogenesis | none | Il-4, CCL3, CCL4, CCL5, PGE2, NO, VEGF, MMP9, bFGF, retinoic acid, TGF-β |
| Tumor endothelial cells [39,40,41] | none | Source of CAFs, attenuation of Tc immune cell response | none | PDGF-B, HGF, EGF, PlGF, VEGF |