Table 1.
Cytokines and their influence on tumor immunity
| Type of cancer | Cytokine | Recognized role in the immune response | Cancer-associated immune response |
|---|---|---|---|
| Ovarian cancer (SKOV-3) | IL-6 | One of the most potent proinflammatory cytokines; activation of the Src kinase family; activation of STAT transcription factors [146, 147] | Inducing polarization of M2 macrophages [148] |
|
Breast cancer (MCF-7) |
Cellular senescence phenotype [149] | ||
| Tumor-derived murine squamous cell carcinoma cell line (PDSC5)/ fibroblasts accelerate stromal supported tumorigenesis (FASST) mouse/ MK16-Ras | Increases in suppressive myeloid cells, accelerates the ability of MDSCs to inhibit anti-tumor T cell responses [150] | ||
| Hepatocellular carcinoma | TAM recruitment [151] | ||
| Tumor-bearing mice (B16 melanoma, MC38 colon carcinoma, or EL4 lymphoma) | Regulates IL-4R expression on MDSCs thereby indirectly inhibiting the release of arginase (Arg1) [90] | ||
| Colorectal cancer | IL-17 | Proinflammatory effect; promotion of congenital activity; activation of neutrophils and T-cells [152] | MDSC recruitment; more pronounced immunosuppressive activity of MDSCs; decrease in the number of CD8+ T cells; positive effect on Treg [153] |
| Esophageal squamous cell carcinoma (ESCC) | Correlation with CXCL2/CXCL3 ligands, enhanced tendency of inflammatory cells to migrate [75] | ||
| Breast cancer | Inhibits MDSC proliferation, promotes MDSC differentiation, reduces levels of TGF-β and IL-10 released by MDSCs and enhances the synthesis of pro-inflammatory factors [101] | ||
|
Breast cancer (MCF-7) |
IL-8 | Proinflammatory effect; involved in lymphocytic infiltration in various cancers [149] | Cellular senescence phenotype [149] |
| Gastric cancer | TNF-α | Biological functions dependent on the type of activated receptors; possible proinflammatory and oncostatic effects [154] |
Induction of PD-L1 expression on mast cells, indirect negative impact on T cell immunity [155] |
|
Ehrlich’s ascites carcinoma (EAC) cells 4T1 mouse breast cancer cells |
M1 TAM marker, prevents polarization towards the M2 subtype [64] | ||
| Lung cancer (NSCLC) | IL-33 | Early inducer of inflammation [156] | Blockade of M2 TAM polarization, decreased recruitment of Tregs in TME; shaping functional immune surveillance [157] |
|
N/A (TME imitating milieu) |
Suppresses or enhances effector functions of cytotoxic/regulatory T cells, differentiation of CD8+ T cells, supports TCR-dependent activation of CD8+ lymphocytes/T lymphocytes [158] | ||
|
Human lung cancer cell line/NSCLC (NCI-H1299 (ATCC® CRL-5803) |
TGF-β | The predominant immunosuppressive activity; regulation of T lymphocyte activity; abolition of anti-tumor immune response [159] | Enhances the antiproliferative effect of MDSCs on T cells, Treg promotion through MDSCs, attenuated antitumor immunity [160] |
| N/A | TAN polarization to N2 subtype [67] | ||
| Esophageal squamous cell carcinoma (ESCC) | TGF-β-dependent Smad3 enhanced PD-1 expression on TILs in the TME [161] | ||
|
Mouse model of pancreatic cancer (LSL-KRasG12D) |
IL-1/IL-1R signaling | Strong proinflammatory effect; alternative action as a transcription factor [162, 163] | Senescence-associated secretory phenotype (SASP) [165] |
| Human mammary cancer-derived cells (MDA-MB-231, MCF-7) | Oncostatin M | Proinflammatory cytokine, induces endothelial activation [164] | Promotes M2 polarization via HIF-1α/ARG1/COX-2 [164] |