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Host CD73 impairs anti-tumor immunity.

Salmi M, Jalkanen S - Oncoimmunology (2012)

Bottom Line: The enzymatic activity of CD73 produces immune-suppressing adenosine.Pharmacological inhibition of CD73 in wild-type mice has similar tumor-suppressing effects.Host CD73 on leukocytes and endothelial cells is thus detrimental for the anti-tumor immunity.

View Article: PubMed Central - PubMed

Affiliation: MediCity Research Laboratory; University of Turku; Turku, Finland ; Department of Medical Biochemistry and Genetics; University of Turku; Turku, Finland ; National Institute of Health and Welfare; Tykistökatu; Turku, Finland.

ABSTRACT
The enzymatic activity of CD73 produces immune-suppressing adenosine. In CD73 deficient hosts, tumor growth and tumor infiltration by Tregs and type 2 immunosuppressive macrophages is reduced. Pharmacological inhibition of CD73 in wild-type mice has similar tumor-suppressing effects. Host CD73 on leukocytes and endothelial cells is thus detrimental for the anti-tumor immunity.

No MeSH data available.


Related in: MedlinePlus

The CD73 on hematopoetic and non-hematopotic cells of the host regulates anti-tumor immunity. The enzymatic activity CD73 is depicted at the top. The involvement of endothelial and leukocyte CD73 in leukocyte extravasation and immune suppression in wild-type and CD73-deficient mice are illustrated. CD73 regulates recruitment of both CD73-positive and -negative leukocytes by modulating the endothelial adhesion molecules and permeability, and CD73 may also have direct adhesive functions. Immune suppression is mainly mediated through the production of adenosine. In addition, certain cancer types express CD73, and it augments the migration of these malignant cells and further renders the tumor microenvironment more immune-suppressing.
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Figure 1: The CD73 on hematopoetic and non-hematopotic cells of the host regulates anti-tumor immunity. The enzymatic activity CD73 is depicted at the top. The involvement of endothelial and leukocyte CD73 in leukocyte extravasation and immune suppression in wild-type and CD73-deficient mice are illustrated. CD73 regulates recruitment of both CD73-positive and -negative leukocytes by modulating the endothelial adhesion molecules and permeability, and CD73 may also have direct adhesive functions. Immune suppression is mainly mediated through the production of adenosine. In addition, certain cancer types express CD73, and it augments the migration of these malignant cells and further renders the tumor microenvironment more immune-suppressing.

Mentions: CD73/ecto-5′-nucleotidase is a cell-surface protein expressed on a subset of leukocytes, including CD4+CD25+FoxP3+ Tregs, vascular and lymphatic endothelial cells and certain epithelial cells.1 It is an ecto-enzyme, which dephosphorylates extracellular AMP into adenosine (Fig. 1).2-4 This reaction is an integral part of the adenosinergic signaling pathway that encompasses the following sequential hydrolyzing reactions: ATP → ADP → AMP → adenosine → inosine. ATP and ADP generally give rise to pro-inflammatory signals via purinergic P2X and P2Y receptors. Adenosine, in contrast, binds to adenosine receptors and evokes anti-inflammatory responses. The enzymatic activity of CD73 is involved in the regulation of leukocyte extravasation, vascular barrier function, and immunosuppressive functions of Tregs, which are all relevant to tumor immunity.


Host CD73 impairs anti-tumor immunity.

Salmi M, Jalkanen S - Oncoimmunology (2012)

The CD73 on hematopoetic and non-hematopotic cells of the host regulates anti-tumor immunity. The enzymatic activity CD73 is depicted at the top. The involvement of endothelial and leukocyte CD73 in leukocyte extravasation and immune suppression in wild-type and CD73-deficient mice are illustrated. CD73 regulates recruitment of both CD73-positive and -negative leukocytes by modulating the endothelial adhesion molecules and permeability, and CD73 may also have direct adhesive functions. Immune suppression is mainly mediated through the production of adenosine. In addition, certain cancer types express CD73, and it augments the migration of these malignant cells and further renders the tumor microenvironment more immune-suppressing.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3376983&req=5

Figure 1: The CD73 on hematopoetic and non-hematopotic cells of the host regulates anti-tumor immunity. The enzymatic activity CD73 is depicted at the top. The involvement of endothelial and leukocyte CD73 in leukocyte extravasation and immune suppression in wild-type and CD73-deficient mice are illustrated. CD73 regulates recruitment of both CD73-positive and -negative leukocytes by modulating the endothelial adhesion molecules and permeability, and CD73 may also have direct adhesive functions. Immune suppression is mainly mediated through the production of adenosine. In addition, certain cancer types express CD73, and it augments the migration of these malignant cells and further renders the tumor microenvironment more immune-suppressing.
Mentions: CD73/ecto-5′-nucleotidase is a cell-surface protein expressed on a subset of leukocytes, including CD4+CD25+FoxP3+ Tregs, vascular and lymphatic endothelial cells and certain epithelial cells.1 It is an ecto-enzyme, which dephosphorylates extracellular AMP into adenosine (Fig. 1).2-4 This reaction is an integral part of the adenosinergic signaling pathway that encompasses the following sequential hydrolyzing reactions: ATP → ADP → AMP → adenosine → inosine. ATP and ADP generally give rise to pro-inflammatory signals via purinergic P2X and P2Y receptors. Adenosine, in contrast, binds to adenosine receptors and evokes anti-inflammatory responses. The enzymatic activity of CD73 is involved in the regulation of leukocyte extravasation, vascular barrier function, and immunosuppressive functions of Tregs, which are all relevant to tumor immunity.

Bottom Line: The enzymatic activity of CD73 produces immune-suppressing adenosine.Pharmacological inhibition of CD73 in wild-type mice has similar tumor-suppressing effects.Host CD73 on leukocytes and endothelial cells is thus detrimental for the anti-tumor immunity.

View Article: PubMed Central - PubMed

Affiliation: MediCity Research Laboratory; University of Turku; Turku, Finland ; Department of Medical Biochemistry and Genetics; University of Turku; Turku, Finland ; National Institute of Health and Welfare; Tykistökatu; Turku, Finland.

ABSTRACT
The enzymatic activity of CD73 produces immune-suppressing adenosine. In CD73 deficient hosts, tumor growth and tumor infiltration by Tregs and type 2 immunosuppressive macrophages is reduced. Pharmacological inhibition of CD73 in wild-type mice has similar tumor-suppressing effects. Host CD73 on leukocytes and endothelial cells is thus detrimental for the anti-tumor immunity.

No MeSH data available.


Related in: MedlinePlus