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IL-33/ST2 axis in innate and acquired immunity to tumors.

Jovanovic IP, Pejnovic NN, Radosavljevic GD, Arsenijevic NN, Lukic ML - Oncoimmunology (2012)

Bottom Line: Interleukin-33, a ligand for ST2/T1, has an important role in allergy, autoimmunity and inflammation.The role of IL-33/ST2 axis in cancer is not elucidated.Using metastatic breast cancer model we provide evidence that lack of ST2 signaling led to reduced tumor growth and metastasis and enhanced anti-tumor immunity.

View Article: PubMed Central - PubMed

Affiliation: Center for Molecular Medicine and Stem Cell Research; Faculty of Medicine; University of Kragujevac; Kragulevac, Serbia.

ABSTRACT
Interleukin-33, a ligand for ST2/T1, has an important role in allergy, autoimmunity and inflammation. The role of IL-33/ST2 axis in cancer is not elucidated. Using metastatic breast cancer model we provide evidence that lack of ST2 signaling led to reduced tumor growth and metastasis and enhanced anti-tumor immunity.

No MeSH data available.


Related in: MedlinePlus

Figure 1. Hypothetical role of IL-33/ST2 axis in tumor growth and progression based on mouse mammary adenocarcinoma 4T1 cancer model. (A) The effects of endogenous and also exogenous IL-33 in tumor-bearing hosts. IL-33 via its receptor ST2L activates Th2-polarized cells and generates relatively immature dendritic cells that do not produce IL-12p70. Subsequently, ST2 signaling could possibly enhance production of thymic stromal lymphopoietin (TSLP) by tumor cells which by upregulating OX40L on dendritic cells lead to induction of IL-4, and more importantly immunosuppressive IL-10 and IL-13 producing Th2-cells that promote cancer escape. Immature dendritic cells induce T regs that contribute to an immunosuppressive environment and facilitate metastasis. (B) In the absence of ST2 (IL-33 receptor), IL-33 produced by epithelial cells and possibly tumor cells does not lead to the activation of Th2-associated immunosuppressive response. Concomitantly, IL-12 produced by classically activated M1 macrophages lead to the maturation of DC, strong IFN-γ production by Th1 cells which activate tumoricidal NK, NKT cells and CD8+ T cytotoxic lymphocytes.
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Figure 1: Figure 1. Hypothetical role of IL-33/ST2 axis in tumor growth and progression based on mouse mammary adenocarcinoma 4T1 cancer model. (A) The effects of endogenous and also exogenous IL-33 in tumor-bearing hosts. IL-33 via its receptor ST2L activates Th2-polarized cells and generates relatively immature dendritic cells that do not produce IL-12p70. Subsequently, ST2 signaling could possibly enhance production of thymic stromal lymphopoietin (TSLP) by tumor cells which by upregulating OX40L on dendritic cells lead to induction of IL-4, and more importantly immunosuppressive IL-10 and IL-13 producing Th2-cells that promote cancer escape. Immature dendritic cells induce T regs that contribute to an immunosuppressive environment and facilitate metastasis. (B) In the absence of ST2 (IL-33 receptor), IL-33 produced by epithelial cells and possibly tumor cells does not lead to the activation of Th2-associated immunosuppressive response. Concomitantly, IL-12 produced by classically activated M1 macrophages lead to the maturation of DC, strong IFN-γ production by Th1 cells which activate tumoricidal NK, NKT cells and CD8+ T cytotoxic lymphocytes.

Mentions: Based on our findings it could be speculated that in the absence of ST2 immunosuppressive Th2-type immune response cannot be enhanced in the presence of IL-33 from epithelial, endothelial or possibly tumor cells. In this setting, IL-12 produced by classically activated M1 macrophages promote maturation of DCs and consequently strong Th1/Th17 response that activate tumoricidal NK, NKT cells and CD8+ T cytotoxic lymphocytes (Fig. 1B). Hypothetically, if IL-33 is overexpressed either endogenously or exogenously, its binding to ST2L activates Th2 cells and promotes generation of relatively immature dendritic cells that do not produce IL-12p70 (Fig. 1A). Immature dendritic cells promote generation of T regs and therefore facilitate tumor progression and metastasis. In addition, ST2 signaling could possibly induce the production of thymic stromal lymphopoietin (TSLP) by tumor cells. TSLP is known to upregulate OX40L on dendritic cells and induce IL-4 and more importantly immunosuppressive IL-10 and IL-13 producing Th2-cells that promote cancer escape.10


IL-33/ST2 axis in innate and acquired immunity to tumors.

Jovanovic IP, Pejnovic NN, Radosavljevic GD, Arsenijevic NN, Lukic ML - Oncoimmunology (2012)

Figure 1. Hypothetical role of IL-33/ST2 axis in tumor growth and progression based on mouse mammary adenocarcinoma 4T1 cancer model. (A) The effects of endogenous and also exogenous IL-33 in tumor-bearing hosts. IL-33 via its receptor ST2L activates Th2-polarized cells and generates relatively immature dendritic cells that do not produce IL-12p70. Subsequently, ST2 signaling could possibly enhance production of thymic stromal lymphopoietin (TSLP) by tumor cells which by upregulating OX40L on dendritic cells lead to induction of IL-4, and more importantly immunosuppressive IL-10 and IL-13 producing Th2-cells that promote cancer escape. Immature dendritic cells induce T regs that contribute to an immunosuppressive environment and facilitate metastasis. (B) In the absence of ST2 (IL-33 receptor), IL-33 produced by epithelial cells and possibly tumor cells does not lead to the activation of Th2-associated immunosuppressive response. Concomitantly, IL-12 produced by classically activated M1 macrophages lead to the maturation of DC, strong IFN-γ production by Th1 cells which activate tumoricidal NK, NKT cells and CD8+ T cytotoxic lymphocytes.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3376988&req=5

Figure 1: Figure 1. Hypothetical role of IL-33/ST2 axis in tumor growth and progression based on mouse mammary adenocarcinoma 4T1 cancer model. (A) The effects of endogenous and also exogenous IL-33 in tumor-bearing hosts. IL-33 via its receptor ST2L activates Th2-polarized cells and generates relatively immature dendritic cells that do not produce IL-12p70. Subsequently, ST2 signaling could possibly enhance production of thymic stromal lymphopoietin (TSLP) by tumor cells which by upregulating OX40L on dendritic cells lead to induction of IL-4, and more importantly immunosuppressive IL-10 and IL-13 producing Th2-cells that promote cancer escape. Immature dendritic cells induce T regs that contribute to an immunosuppressive environment and facilitate metastasis. (B) In the absence of ST2 (IL-33 receptor), IL-33 produced by epithelial cells and possibly tumor cells does not lead to the activation of Th2-associated immunosuppressive response. Concomitantly, IL-12 produced by classically activated M1 macrophages lead to the maturation of DC, strong IFN-γ production by Th1 cells which activate tumoricidal NK, NKT cells and CD8+ T cytotoxic lymphocytes.
Mentions: Based on our findings it could be speculated that in the absence of ST2 immunosuppressive Th2-type immune response cannot be enhanced in the presence of IL-33 from epithelial, endothelial or possibly tumor cells. In this setting, IL-12 produced by classically activated M1 macrophages promote maturation of DCs and consequently strong Th1/Th17 response that activate tumoricidal NK, NKT cells and CD8+ T cytotoxic lymphocytes (Fig. 1B). Hypothetically, if IL-33 is overexpressed either endogenously or exogenously, its binding to ST2L activates Th2 cells and promotes generation of relatively immature dendritic cells that do not produce IL-12p70 (Fig. 1A). Immature dendritic cells promote generation of T regs and therefore facilitate tumor progression and metastasis. In addition, ST2 signaling could possibly induce the production of thymic stromal lymphopoietin (TSLP) by tumor cells. TSLP is known to upregulate OX40L on dendritic cells and induce IL-4 and more importantly immunosuppressive IL-10 and IL-13 producing Th2-cells that promote cancer escape.10

Bottom Line: Interleukin-33, a ligand for ST2/T1, has an important role in allergy, autoimmunity and inflammation.The role of IL-33/ST2 axis in cancer is not elucidated.Using metastatic breast cancer model we provide evidence that lack of ST2 signaling led to reduced tumor growth and metastasis and enhanced anti-tumor immunity.

View Article: PubMed Central - PubMed

Affiliation: Center for Molecular Medicine and Stem Cell Research; Faculty of Medicine; University of Kragujevac; Kragulevac, Serbia.

ABSTRACT
Interleukin-33, a ligand for ST2/T1, has an important role in allergy, autoimmunity and inflammation. The role of IL-33/ST2 axis in cancer is not elucidated. Using metastatic breast cancer model we provide evidence that lack of ST2 signaling led to reduced tumor growth and metastasis and enhanced anti-tumor immunity.

No MeSH data available.


Related in: MedlinePlus