The ectonucleotidases CD39 and CD73: new targets for cancer immunotherapy

Cancer cells are able to induce immune suppressive pathways, which prevents cancer cells to be recognised by the host’s immune response as altered or harmful. Cancer immunotherapy promotes the body’s own immune system to fight cancer. Monoclonal antibodies, cancer vaccines, nonspecific cancer immunotherapies and immune checkpoint inhibitors are used in cancer immunotherapy. Two prominent immune checkpoints PD1 and CTLA4 are involved in immune suppression by cancer cells. More recently, CD39 and CD73 have been recognised as alternate druggable immune checkpoints. CD39 and CD73 are ectoenzymes present on the surface of different immune cells. CD39 and CD73 cooperate in the conversion of extracellular ATP into adenosine. Normally intracellular ATP serves to provide energy needed for cell processes, whereas extracellular ATP functions as an immune regulator that reduces inflammation by inhibiting the release of pro-inflammatory cytokines. Since CD39 and CD73 are crucial for the conversion of ATP into adenosine, therapeutic blocking of the enzymatic activity of CD39 and CD73 may be of use for cancer immunotherapy. In this bachelor thesis I will discuss the role of ectonucleotidases CD39 and CD73 in cancer and their therapeutic potential as druggable targets in cancer immunotherapy.