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CD73

CD73 can promote adenosine production and release into the tumor microenvironment, reducing immune activity. Inhibition of CD73 may stimulate T-cell activity.

Expression and normal function

CD73 is a cell-surface enzyme on regulatory T cells (Tregs)¹
CD73 is critical for the conversion of immune-activating ATP into immunosuppressive adenosine, the release of which helps Tregs shut down immune activity^1-3*

CD39 catalyzes ATP or ADP into AMP, which is then converted by CD73 to adenosine, which may mediate immunosuppressive effects on T cells.⁵

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Role in cancer

Cancer exploits the function of CD73 to reduce antitumor immunity. Similar to Tregs, tumor cells express CD73 and release adenosine into the tumor microenvironment^4-6

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Preclinical evidence

In cellular studies, adenosine powerfully inhibits the antitumor immune response, including cytokine proliferation and production¹
Preclinical research has identified tumor-derived CD73 as a contributor to immune escape in cancer, and inhibition of CD73 activity can stimulate T-cell activity⁷
Preclinical studies have also shown that the blockade of CD73 in combination with checkpoint inhibitors can enhance antitumor activity⁸

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How does CD73 generate a suppressive environment?

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REFERENCES–CD73

1. Kobie JJ, Shah PR, Yang L, Rebhahn JA, Fowell DJ, Mosmann TR. T regulatory and primed uncommitted CD4 T cells express CD73, which suppresses effector CD4 T cells by converting 5’-adenosine monophosphate to adenosine. J Immunol. 2006;177(10):6780-6786. 2. Deaglio S, Dwyer KM, Gao W, et al. Adenosine generation catalyzed by CD39 and CD73 expressed on regulatory T cells mediates immune suppression. J Exp Med. 2007;204(6):1257-1265. 3. Picher M, Burch LH, Hirsh AJ, Spychala J, Boucher RC. Ecto 5’-nucleotidase and nonspecific alkaline phosphatase. J Biol Chem. 2003;278(15):13468-13479. 4. Häusler SF, del Barrio IM, Strohschein J, et al. Ectonucleotidases CD39 and CD73 on OvCA cells are potent adenosine-generating enzymes responsible for adenosine receptor 2A-dependent suppression of T cell function and NK cell cytotoxicity. Cancer Immunol Immunother. 2011;60(10):1405-1418. 5. Serra S, Horenstein AL, Vaisitti T, et al. CD73-generated extracellular adenosine in chronic lymphocytic leukemia creates local conditions counteracting drug-induced cell death. Blood. 2011;118(23):6141-6152. 6. Ohta A, Gorelik E, Prasad SJ, et al. A2A adenosine receptor protects tumors from antitumor T cells. Proc Natl Acad Sci USA. 2006;103(35):13132-13137. 7. Stagg J, Divisekera U, McLaughlin N, et al. Anti-CD73 antibody therapy inhibits breast tumor growth and metastasis. Proc Natl Acad Sci USA. 2010;107(4):1547-1552. 8. Allard B, Pommey S, Smyth MJ, Stagg J. Targeting CD73 enhances the antitumor activity of anti-PD-1 and anti-CTLA-4 mAbs. Clin Cancer Res. 2013;19(20):5626-5635.