CD73 can promote adenosine production and release into the tumor microenvironment, reducing immune activity. Inhibition of CD73 may stimulate T-cell activity.
CD39 catalyzes ATP or ADP into AMP, which is then converted by CD73 to adenosine, which may mediate immunosuppressive effects on T cells.5
- Cancer exploits the function of CD73 to reduce antitumor immunity. Similar to Tregs, tumor cells express CD73 and release adenosine into the tumor microenvironment4-6
- 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
How does CD73 generate a suppressive environment?
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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