Table 2.

Different cell populations in the tumor microenvironment [7,13,14,15].

Cell Type	Natural Function	Function in Tumor Microenvironment	Produced Substances
			of Anti-Tumor Activity	of Pro-Tumor Activity
HELPER T CELLS	Th1-stimulates dendritic and NK cells. Attracts T lymphocytes.	Th1- blocked by IL-4, IL-10, TGF-β, Treg, Th2, M2 Th2-. Inhibition of Th1. Stimulation of M2 population of macrophages.	TNF-α, IL-12, IL-17,IL-18, IL-21, IL-27.	Th17 lymphocytes can transform into Treg lymphocytes.
REGULATORY T CELLS	Protection against autoimmunity from autoreactive T lymphocytes.	Stimulating immune tolerance. Immunosuppression. Inhibition of the immune response.	IL-10, TGF-β, adenosine, PGE2, IL-35.	TGF-β, IL-2, IL-10, IL-35.
CYTOTOXIC T CELLS	Cytotoxic. Stimulation of other immune cells to infiltrate the tumor.	Inhibition of the cytotoxic function by binding to PD-L1.	Perforins. Granzymes IL-2, TNF-α, IFN-γ.	------
MACROPHAGES	Destruction, phagocytosis of abnormal cells. Inducing inflammation.	TAM2: Protumor. Inhibition of the inflammatory process.	IFN-γ, IL-12, GM-CSF.	IL-10, TGF-β, EGF, FGF, VEGF, MMP CCL2, CCL5, CCL3, CCL8, CCL22.
NEUTROPHILS	Phagocytosis. ADCC. Stimulation of CD8 + lymphocytes, NK cells.	N1: Phagocytosis. Stimulation of apoptosis N2: Angiogenesis. Stimulation of the inflammatory process in the tumor.	TNF-α, IFN- γ.	TGF-β, MPO, MMP9, HGF, VEGF
B CELLS	Presenting antigens. Complement activation. Antibody production.	Supporting angiogenesis. -inhibition of anti-cancer activities. Stimulation of Treg.	IL-2.	IL-10, TGF-β.
CANCER ASSOCIATED FIBROBLASTS (CAF)	--------	Secreting growth factors. Causing inflammation.	--------	CXCL1, CXCL2, CXCL3, CXCL12, CCL2, CCL5, CCL17, IL-8, GM-CSF TGF-β, IL-6, exosomes, HGF, IGF, CTGF.
NATURAL KILLER CELLS (NK)	Cytotoxic. Immune supervision. Stimulation of T and DC lymphocytes.	--------	IL-2, IL-6, 12, 15, IFN-γ, TNF-α, GM-CSF, CCL-5.	--------
DENDRITIC CELLS (DC)	Presentation of antigens. Influences the differentiation of helper and regulatory lymphocytes. Cytotoxic function.	Presence on the surface of PD-L1, Impaired antigen presentation, maturation and tumor infiltration.	IL-6, IL-8, IL-12, IL-15.	--------
CANCER ASSOCIATED ADIPOCYTES (CAA)	Production and storage of simple fats (triglycerides).	Secretion of adipokines. They cause changes in the metabolism of cancer cells and remodel the ECM.	--------	Adipokines: leptin, hepatocyte growth factors IL-1β.
MYELOID-DERIVED SUPPRESSOR CELLS (MDSC)	--------	Suppression of the immune response.	--------	IL-4, CCL3, CCL4, CCL5, PGE2, NO.

IL, interleukin; Th1, helper T lymphocyte 1; Th2, helper T lymphocyte 2; TGF-β, transforming growth factor beta; TNF-α, tumor necrosis factor alfa; PGE2, prostaglandin E2; PD-L, programmed death cell ligand 1; TAM, tumor-associated macrophages; IFN-γ, interferon gamma; GM-CSF, granulocyte-macrophage colony-stimulating factor; EGF, epidermal growth factor; FGF, fibroblast growth factor; VEGF, vascular endothelial growth factor; MMP, matrix metalloproteinases; CCL, chemokines; ADCC, antibody-dependent cell cytotoxicity; MPO, myeloperoxidase; HGF, hepatocyte growth factor; IGF, insulin-like growth factor; CTGF, connective tissue growth factor; ECM, extracellular matrix; NO, nitric oxide.