CD73 promotes tumor growth and metastasis

Abstract

Our recent data and that of others demonstrate that both tumor and host CD73-generated adenosine promote tumor growth and metastasis in a multifactorial manner. Results with small molecule inhibitors or monoclonal antibodies against CD73 in multiple tumor models suggest that CD73 is a previously unappreciated important target for effective cancer therapy.

Figure 1.

Immune actions of CD73-generated adenosine in the tumor microenvironment. The sequential action of cellular ecto-ATPase (CD39) and/or ecto-5′-nucleotidase (CD73) represents a primary pathway of extracellular adenosine generation in the tumor microenvironment. Recent studies including our own work suggest that both tumor and host CD73 promote tumor growth and metastasis. CD73 has distinct roles in hematopoietic and nonhematopoietic cells in limiting antitumor T cell immunity through its etco-enzymatic activity. The mechanism by which nonhematopoietic CD73 promotes lung metastasis remains unclear. Meanwhile, the impact of CD73-generated adenosine on differentiation and function of dendritic cells (DCs) and macrophages (MØ), and natural killer (NK) cell proliferation and cytolytic function requires further investigation.