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Table 3 Regulation and role of diverse immune cells in tumor microenvironment

From: Crosstalk of pyroptosis and cytokine in the tumor microenvironment: from mechanisms to clinical implication

Type

Featured cytokines

Stimulus

Signal pathways

Role in metastasis

Target drugs/agents

Reference

MDSC

IL-6, IL-1b, GM-

CSF, G-CSF, VEGF, and MCP-1

IL-6, IL-1b, GM-

CSF, G-CSF, VEGF, and MCP-1

EZH2/NF-KB signaling, CCL26/CX3CR1, STAT3 pathway and NF-κB pathway

Promotion of immune suppression, Enhancement of angiogenesis and vascular permeability and Induction of tumor-induced immunosuppression

Sildenafil, Pexidartinib, AZD5069, Epacadostat

[192,193,194,195]

CAFs

TGF-β, HGF, PDGF, FGF-2, SDF-1, ROS

TGF-β, HGF, PDGF, FGF-2, SDF-1, ROS

IL-6/STA T3 pathway, TGF-β Signaling Pathway, Wnt/β-catenin Signaling Pathway, HGF/c-Met Signaling Pathway

Promotion of tumor growth and metastasis, Modulation of tumor microenvironment, Induction of immune evasion and Involvement in EMT process

FAP Inhibitors, Vismodegib, Galunisertib (LY2157299), Plerixafor (AMD3100)

[196,197,198,199]

Treg cells

IL-2, IL-10, TGF-β, IL-35, TNF-α and IFN-γ

interaction of TCR

with IL-10 and TGF-b signaling

FoxP3 pathway, CTLA-4 pathway, IDO access, IL-2/STAT5 pathway:

Immunosuppressive, Promote immune evasion, Hyperactivity of

Treg cells in tumor cell promotes tumor invasiveness and leads to a compromised T-cell immune response through Cytokines

Galunisertib (LY2157299), Ipilimumab, Epacadostat, Daclizumab, MEDI6383

[200,201,202,203]

TAM

IL-6, VEGF, Arg1, IL-10, TGF-β, IL-4, IL-13, CSF-1, CCL2, CXCL12, CTG, IDO, CCL17, CCL18, and CCL22

IL-4, IL-13, CSF-1, CCL2, CXCL12, and CTG

STAT3, NF-κB, TGF-β/Smad, PI3K/AKT, MAPK, HIF-1α and PD-1/PD-L1, CSF-1/CSF-1R

Promote tumor growth, promote tumor metastasis, suppress anti-tumor immune response and promote inflammation and immune regulation

Pexidartinib (PLX3397), IPI-549, Nivolumab

[204,205,206,207,208]

TANs

IL-8, VEGF, MMP-9, TGF-β, ROS, proteinases, IFN-γ

TGF-β

JAK/STAT, NF-κB, PI3K/AKT

Promote tumor growth, suppress immune response, direct tumor cell killing, and activate antitumor immunity

BMS-986,253, Galunisertib (LY2157299)

[209,210,211,212]

  1. Abbreviations: IL-6 Interleukin-6, IL-1b Interleukin-1 beta, GM-CSF Granulocyte-Macrophage Colony-Stimulating Factor, G-CSF Granulocyte Colony-Stimulating Factor, VEGF Vascular Endothelial Growth Factor, MCP-1 Monocyte Chemoattractant Protein-1, HGF Hepatocyte growth factor, PDGF Platelet-derived growth factor, FGF-2 Fibroblast growth factor 2, SDF-1 Stromal-derived factor-1, ROS Reactive Oxygen Species, MDSC Myeloid-Derived Suppressor Cells, CAFs Cancer-Associated Fibroblasts, TAM Tumor-Associated Macrophages, TANs Tumor-Associated Neutrophils, IL-2 Interleukin-2, TGF-β Transforming Growth Factor Beta, IL-35 Interleukin-35, TNF-α Tumor Necrosis Factor Alpha, Arg1 Arginase 1, IL-10 Interleukin-10, IL-4 Interleukin-4, IL-13 Interleukin-13, CSF-1 Colony Stimulating Factor 1, CCL2 Chemokine (C-C motif) Ligand 2, CXCL12 Chemokine (C-X-C motif) Ligand 12, CTG Common Terminology for Genetics, IDO Indoleamine 2,3-Dioxygenase, CCL17 Chemokine (C-C motif) Ligand 17, CCL18 Chemokine (C-C motif) Ligand 18, CCL22 Chemokine (C-C motif) Ligand 22, CCR6 Chemokine (C-C motif) Receptor 6, CCL20 Chemokine (C-C motif) Ligand 20, IL-8 Interleukin 8, VEGF Vascular Endothelial Growth Factor, MMP-9 Matrix Metalloproteinase 9, IFN-γ Interferon gamma, TCR T-cell Receptor, EZH2 Enhancer of Zeste Homolog 2, NF-KB Nuclear Factor-Kappa B, CCL26 Chemokine Ligand 26, CX3CR1 CXC Chemokine Receptor 1, STAT3 Signal Transducer and Activator of Transcription 3, IL-6 Interleukin 6, HGF Hepatocyte Growth Factor, c-Met Cellular-Mesenchymal-Epithelial Transition Factor, FoxP3 Forkhead Box 3, CTLA-4 Cytotoxic T-Lymphocyte-Associated Protein 4, IL-2 Interleukin 2, STAT5 Signal Transducer and Activator of Transcription 5, Smad SMA and MAD-related protein PI3K/AKT Phosphatidylinositol-3 Kinase/Protein Kinase B, MAPK Mitogen-Activated Protein Kinase, HIF-1α Hypoxia-Inducible Factor-1 alpha, PD-1 Programmed Cell Death Protein-1, PD-L1 Programmed Death-Ligand 1, CSF-1 Colony-Stimulating Factor 1, CSF-1R Colony-Stimulating Factor 1 Receptor, JAK/STAT Janus Kinase/Signal Transducer and Activator of Transcription, Treg regulatory T
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Molecular Cancer

ISSN: 1476-4598