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Table 1 Different cell populations exhibit distinct functions within the tumor microenvironment

From: Effect of tumor microenvironment on pathogenesis of the head and neck squamous cell carcinoma: a systematic review

Cell type

Markers (human)

Increased production

Activity

Function

Ref.

M1 TAMs

CD68+

IL-12, IL-23, TNF-α, CCL-5, CXCL9, CXCL10, CXCL5

anti-tumor

contribution to the Th1 response, inhibition of proliferation, cytotoxic activity

[44,45,46]

M2 TAMs

CD68+

IL-1ra, IL-10, TGF-β, arginase-1

pro-tumor

promotion of tumor progression, angiogenesis, suppression of T cell antitumor immune response

[47,48,49,50,51,52,53]

N1 TANs

CD11b+, CD14+, CD15+, CD16+, CD62L+, CD66b+

ICAM1, TNF-α

anti-tumor

cytotoxic activity, increased NET formation

[79]

N2 TANs

CD11b+, CD14+, CD15+, CD16+, CD62L+, CD66b+

CXCR4, VEGF, MMP-9

pro-tumor

promotion of angiogenesis, invasion

[77, 78]

MCs

CD117+, CD203c+, FcεRI+

histamine, heparin, chondroitin sulfate E, PGD2, tryptase, chymase, CPA1, LTC4, GM-CSF, MMPs, IL-4, TNF-α, cathepsin G

pro-tumor

promotion of angiogenesis, ECM degradation, stimulation of cancer cell proliferation, recruitment of immune cells

[120, 123,124,125,126,127]

MDSCs

CD11b+, CD33+, CD14+, CD15+, CD16+, HLA-DR-

NO, ROS, iNOS, arginase-1, PD-L1, MMP-9

pro-tumor

immunosuppression, inhibition of T cell activation and proliferation, promotion of angiogenesis, degradation of ECM

[82,83,84,85,86,87,88, 94, 95]

NK cells

CD3-, CD16+, CD56+

IFN-γ, TNF-α, GM-SCF,

IL-5, IL-8, IL-10, IL-13, CCL2, CCL3, CCL4, CCL5, CXCL10

anti-tumor

cytotoxic activity without prior antigen presentation, modulation of adaptive immune response

[132,133,134,135, 138,139,140,141]

NKT cells

CD3+,CD56+, CD161+, CD1a+, CD16+

IFN-γ, TNF-α, GM-CSF, TGF-β, IL-2 , IL-4, IL-5,

IL-6, IL-10, IL-13, IL-17A

anti-tumor

cytotoxic activity, antigen-specific immunological memory

[142,143,144,145,146]

Tregs

CD4+, CD25+, FOXP3+

IL-10, IL-35, TGF-β, VEGF

pro-tumor

immunosuppression, promotion of angiogenesis

[97,98,99, 101, 102]

Platelets

CD41+, CD42a+, CD42b+, CD61+

ADP, ATP, calcium, 5-HT, CD63, LAMP1/2, GP-Ib,

P-selectin, integrin αII-β3, fibrinogen, vitronectin, thrombospondin, fibronectin, VWF, MMPs, GLUT3

pro-tumor

thrombosis, wound healing, maintaining of homeostasis, vasoconstriction, promotion of cell proliferation, immunoevasion by platelet aggregation

[105,106,107, 109,110,111, 113,114,115,116]

CAFs

α-SMA+, FAP+,

FSP-1+, CD33-, absent cytokeratin

EGF, HGF, VEGF, CXCL12, CXCL14, CCL5, CCL7, IL-6, IL-17A, MMPs

pro-tumor

stimulation of tumor growth, invasion, angiogenesis, metastasis, induction of chemo- and radio-resistance, ECM degradation

[12,13,14,15,16,17,18,19]

  1. Abbreviations: TAMs tumor-associated macrophages, TANs tumor-associated neutrophils, MCs mast cells, MDSCs myeloid-derived suppressor cells, NK natural killer cells, NKT natural killer T cells, Tregs regulatory T cells, CAFs cancer-associated fibroblasts