Table 1: Potential pro- and antitumorigenic roles of cytokines.

CytokineProtumorigenic roleAntitumorigenic roleUnspecified yet role in tumorigenesisReferences

IL-1 (α and β) Tumor growth, invasion and metastasis, mainly through the action of IL-1β in promoting local inflammatory responses as well as angiogenesis. Restraint of tumor growth through activation of innate and specific immune effector mechanisms mainly through the action of IL-1α.[17]

IL-2(i) Stimulates growth, differentiation, and survival of cytotoxic T cells
(ii) Induces differentiation and proliferation of NK cells
[53]

IL-3Stimulates the differentiation and growth of multipotent hematopoietic stem cells[54]

IL-4(i) Decreases the production of Th1 cells, macrophages, and IFN-gamma
(ii) Has been shown to drive dedifferentiation, mitogenesis and metastasis in rhabdomyosarcoma
Stimulation of activated B-cell and T-cell proliferation, and differentiation of CD4+ T-cells into Th2 cellsIgE and class II MHC expression on B cells[55]

IL-5(i) Stimulates B cell growth
(ii) Stimulates eosinophil growth and function
[56]

IL-6(i) Promotion of tumor cell proliferation and inhibition of their apoptosis through activation of STAT-3.
(ii) Facilitation of senescence evasion in high-grade preneoplastic or cancerous cells through mechanisms of SASP.
(iii) Favours metastasis
(i) Mediator of the acute phase response
(ii) Induction of senescence in normal or low grade preneoplastic cells.
[25, 44]

IL-7Stimulates proliferation of B cells, T cells, and NK cellsStimulates the differentiation of multipotent hematopoietic stem cells[57]

IL-8 Significant role in tumor growth, angiogenesis, epithelial to mesenchymal transition (EMT) and invasiveness(i) Induction of chemotaxis in its target cells (neutrophils, granulocytes)
(ii) Induction of senescence in normal or low-grade preneoplastic cells.
[43, 44]

IL-9(i) Potential role in tumorigenesis due to antiapoptotic and growth factor activities
(ii) Deregulated IL-9 response may lead to malignant transformation through Jak/STAT activation
Regulation of hematopoietic cells[58]

IL-10Potential tumor promoting activity through activation of STAT3 and consequent upregulation of BCL-2 or BCL-XL antiapoptotic genes.(i) Enhances B-cell survival, proliferation, and antibody production.
(ii) Inhibition of tumor development and progression through inhibition of NF-κB activation, TNF-α, IL-6, and IL-12.
(iii) Suppression of angiogenesis through inhibition of the tumor stroma.
[10, 59]

IL-11(i) Regulator of haematopoiesis
(ii) Stimulation of megakaryocyte maturation
[60]

IL-12(i) Stimulates the growth and function of T cells
(ii) Stimulates the production of IFN-γ, TNF-α
(iii) Induces cell-mediated immune responses
(iv) Exhibits antiangiogenic activity
[61]

IL-13 Induces IgE secretion[62]

IL-14 Regulates the growth and proliferation of B cells[63]

IL-15(i) Stimulates growth, differentiation and survival of cytotoxic T cells
(ii) Induces differentiation and proliferation of NK cells
[53]

IL-16Chemoattractant for certain immune cells expressing the cell surface molecule CD4.[64]

IL-17(i) Enhanced tumorigenic role exhibited in several cell lines in mice
(ii) Increases tumor angiogenesis
(iii) Induces increased expression of IL-6
Evidence of tumor cell growth inhibition by means of possible increased immune surveillance.[10, 65, 66]

IL-18(i) Induces cell-mediated immunity
(ii) Induces production of INF-γ
[67]

TNF-α(i) Critical role in overall tumor cell survival by means of NF-κB-dependent antiapoptotic molecules.
(ii) Promotion of angiogenesis and metastasis.
(iii) Suppression of immune surveillance responses to the tumor.
[10]

IFN-γ(i) Produced by cytotoxic CD8+ and CD4+ Th1 T cells
(ii) Exhibits an overall significant tumor inhibitory action.
[1, 7]

TGF-βTumor promoting role at the late stages of carcinogenesisTumor suppressive role in the beginning of carcinogenesis[40]

OPN Implicated in enhanced metastasis and invasion of tumor cells[68]

CCL2(i) Induces the recruitment of macrophages
(ii) Induces angiogenesis and matrix remodeling
(iii) Promotes prostate cancer cell proliferation, migration, invasion, and survival
[69]

CCL21(i) Immune-mediated antitumor response (chemoattraction of B cells and NK cells to the lymph nodes)
(ii) Angiostatic effect
[70, 71]

CCL16Augments the cytotoxic activities of effector T cells[72]

CXCL12(i) Suppress antitumor immunity in the tumor microenvironment
(ii) Regulates trafficking of immature and maturing immune cells
(iii) Promotes angiogenesis
(iv) Facilitates metastasis
[73]

NK cells: Natural Killer cells; IgE: Immunoglobulin E; MHC: Major Histocompatibility Complex; OPN: Osteopontin.