Table 2.
Cytokine profile associated with CRC
| Classification | Function/Effect | Source | Reference | ||
|---|---|---|---|---|---|
| IFN | IFN-I | IFN-α | inhibit virus replication, and enhance the role of MHC-II molecules. Activate DCs and increase the cytolytic activity of macrophages and NK cells, induce IL-15 production, increase T cell survival, and increase the production of stromal-derived vascular inhibitory molecules | activated macrophages, monocytes, and activated T cells | Dunn et al. and Di Franco et al.2,11 |
| IFN-β | Fibroblasts | Dunn et al. and Di Franco et al.2,11 | |||
| IFN-II | IFN-γ | inhibit virus replication, increase the production of MHC-I and MHC-II in cancer cells, increase the production of IL-12 in APC, promote Th1 polarization, and activate macrophages. IFN-γ stimulation leads to nuclear translocation and phosphorylation of STAT1, leading to STAT1-TET2 binding. IFN-γ is an effective inducer of IDO expression and a pathogenic driver of CRC progression | Th1,Tc1,NK cells | Dunn et al., Wang et al., and Du et al.2,14,17 | |
| Interleukin | IL-1F | IL-1α, IL-1β, | enhance the expression of cytokines (such as IL-2 and its receptors) to stimulate T cell activation, enhance B cell proliferation and maturation, NK cytotoxicity, induce the expression of IL-1, IL-6, IL-8, TNF, GM-CSF, and PGE2 in macrophages and the expression of chemokines to play a pro-inflammatory role | monocytes, macrophages, DCs, NK, B cells, endothelial cells | Li et al., Kasprzak, Sharma and Kanneganti195,196,197 |
| IL-18 | induce T cells to produce IFN-γ and enhance NK cytotoxicity | macrophages and DCs | Li et al. and Sharma and Kanneganti195,197 | ||
| IL-36α, IL-36β, IL-36γ | activated monocytes, macrophages, and keratinocytes produce a variety of pro-inflammatory factors to stimulate T cells together | keratinocytes, other barrier tissues, neutrophils | Li et al., Li et al., and Xu et al.195,198,199 | ||
| IL-37 | anti-inflammatory effect | monocytes, macrophages, epithelial cells, activated B cells | Li et al.195 | ||
| IL-38 | N terminus of apoptotic cells | Li et al.195 | |||
| IL-2 family (γc family) | IL-2 | induce the proliferation of activated T cells and activated B cells, enhance NK cells' cytotoxicity, and the monocytes and macrophages' ability to kill tumor cells and bacteria | Th1 | Li et al. and Heys et al.195,200 | |
| IL-4 | induce Th2 cells, stimulate the proliferation of B, T, and mast cells, upregulate B cells, macrophage MHC-II molecules and CD23 of B cells, downregulate IL-12 production to inhibit Th1 differentiation, and enhance macrophage endocytosis, mediates tumor cell proliferation, survival, and metastasis in colon cancer | Th2, Tc2, NK, NKT, γδT, and mast cells | Li et al. and Song et al.195,201 | ||
| IL-13 | inhibit macrophage activation and cytokine secretion, stimulate B cell proliferation, upregulate B cell and monocyte MHC-II class molecules and CD23 expression, and mediate tumor cell proliferation, survival and metastasis of colon cancer | Th2 and mast cells | Song et al.201 | ||
| IL-15 | induce the proliferation of T, NK, and activated B cells and the production of NK and CD8+ T cell factors | T, NK, monocytes, macrophages, DCs, and B cells | Li et al. and Zarogoulidis et al.195,202 | ||
| IL-21 | NK differentiation, B cell activation, stimulation of T cell, Follicular helper T cells (Tfh) directed differentiation and survival | Th | Li et al.195 | ||
| chemokine family | IL-3 | promote growth and differentiation of hematopoietic cell precursors, mast cell growth | T, NK, and mast cells | Li et al.195 | |
| IL-8 | mediate chemotaxis and activation of neutrophils IL-8 modulates not only stemness maintenance but also stemness promotion, such as epithelial-mesenchymal transition |
monocytes, macrophages, and endothelial cells | Kasprzak and Conciatori et al.196,203 | ||
| IL-12/IL-6 family | IL-6 | promote the differentiation of myeloid stem cells, and the differentiation of B cells into plasma cells, induce the expression of acute phase proteins, enhance the proliferation of T cells, and it is vital for Th17 and Tfh-directed differentiation | Th2, monocytes, macrophages, DCs, and bone marrow stromal cells | Kasprzak and Taniguchi and Karin196,204 | |
| IL-12 | induce the proliferation of Th1, CD8+T, γδT, NK and the production of IFN-γ and enhance NK cell and CD8+ T cell cytotoxicity | monocytes, macrophages, DCs, and B cells | Taniguchi and Karin and Engel and Neurath204,205 | ||
| IL-23 | induce Th1 proliferation and IFN-γ production, induce Th17 expansion and survival, induce macrophages to express pro-inflammatory factors (such as IL-1, IL-6, TNF), and inhibit intestinal inflammation | DCs | Taniguchi and Karin and Neurath204,206 | ||
| IL-27 (IL-30) | induce Th1 responses, enhance IFN-γ production | DCs and monocytes | Taniguchi and Karin and Engel and Neurath204,205 | ||
| IL-35 | produce immunosuppressive effects on Th1, Th2, and Th17, stimulating Treg proliferation | Treg | Taniguchi and Karin204 | ||
| IL-10 family | IL-10 | suppress IFN-γ secretion and IL-2 secretion, downregulation of MHC-II molecules and cytokines such as IL-2 production, inhibition of Th1 differentiation, inhibition of T cell proliferation, and enhancement of B cell differentiation | Th, Tc, B cells, monocytes, and macrophages | Li et al. and Landskron et al.195,207 | |
| IL-19 | regulate Th1 activity | monocyte | Li et al.195 | ||
| IL-20 | regulate skin inflammation | monocyte and keratinocyte | Li et al.195 | ||
| IL-22 (IL-TIF) | inhibition of Th2 and secretion of IL-4 | T cells | Li et al. and Wei et al.195,208 | ||
| IL-24 (MDA-7) | induce TNF, IL-1, IL-6 expression and anti-tumor activity | Th2, monocytes, and macrophages | Li et al.195 | ||
| IL-26 | enhance epithelial cell production of IL-8 and IL-10 | T cells and NK cells | Li et al. and Niess et al.195,209 | ||
| IL-17 family | IL-17 | pro-inflammatory effect, stimulate the expression of TNF, IL-1β, IL-6, IL-8, G-CSF and other factors, inhibit intestinal inflammation | T cells | Hurtado et al. and Wu et al.210,211 | |
| IL-25 | induce IL-4, IL-5, IL-13 expression and Th2 related pathological changes | Th1, macrophages, and mast cell | Li et al. and Jou et al.195,212 | ||
| other interleukins | IL-7 | induce differentiation of lymphocytic stem cells into T and B lineage progenitor cells, and activate mature T cells | bone marrow and thymic stromal cells | Zarogoulidis et al.202 | |
| IL-33 | promote inflammatory response and induce Th2-mediated innate and adaptive immune responses | macrophages, DCs, fibroblasts, and mast cell | Jou et al.212 | ||
| growth factor | GM-CFS | stimulate the growth of monocytes, neutrophils, eosinophils, and basophils, and activate macrophages | Th, macrophages, fibroblasts, mast cells, and endothelial cells | Aliper et al.213 | |
| VEGF | promote tumor angiogenesis, and it is closely related to the invasion and metastasis of CRC | endothelial cells, smooth muscle cells, some mesenchymal and stromal cells | Maryam et al.214 | ||
| TGF | TGF | TGF-α | associated with tumor metastasis and invasion | macrophages, brain cells, and keratinocytes | Lee et al.215 |
| TGF-β | pro-inflammatory effects include induction of monocyte and macrophage chemotaxis; anti-inflammatory effects, such as inhibition of lymphocyte proliferation | Th, B cells, macrophages, and mast cells | Lee et al.215 | ||
| TNF | TNF | TNF-α | cause cachexia and tumor cytotoxicity, induce cytokine secretion, and activate macrophages | Th, monocytes, macrophages, DCs, mast cells, NK cells, and B cells | Kasprzak and Landskron et al.196,207 |
| TNF-β | cause tumor cytotoxicity, enhance the endocytosis of neutrophils and macrophages, and participate in the development of lymphoid organs | Th1, Tc | Maryam et al.214 | ||