CD73 in glioblastoma: Where are we now and what are the future directions?

Glioblastoma (GB) is the most aggressive type of brain tumor with heterogeneity, strong invasive ability, and high resistance to therapy due to immunosuppressive mechanisms. CD73 is an overexpressed enzyme in GB that acts via two main mechanisms: (1) CD73 acts as an adhesion protein independent of the enzymatic activity or (2) via the catalyses of AMP to adenosine (ADO) generating a strong modulatory molecule that induces alterations in the tumor cells and in the tumor microenvironment cells (TME). Taken together, CD73 is receiving attention during the last years and studies demonstrated its dual potential benefit as a target to GB therapy. Here, we review the roles of CD73 and P1 receptors (ADO receptors) in GB, the impact of CD73 in the immune interactions between tumor and other immune cells, the proposed therapeutic strategies based on CD73 regulation, and discuss the gap in knowledge and further directions to bring this approach from preclinical to clinical use.

Automated summary

Glioblastoma (GB), the most aggressive brain tumor, shows heterogeneity, strong invasive ability, and high resistance to therapy due to immunosuppressive mechanisms. CD73, an overexpressed enzyme in GB, acts through adhesion protein activity or AMP catalysis to adenosine (ADO) generation, inducing changes in tumor cells and tumor microenvironment cells (TME). CD73 is considered a potential target for GB therapy. This review explores the roles of CD73 and ADO receptors in GB, their impact on immune interactions, therapeutic strategies, and the necessary steps to move this approach from preclinical to clinical use.