Complex tumor-immune cell interactions
Complex mechanisms of action of adenosinergic signaling might not be limited to direct effects on the tumor cell. Additional indirect effects of adenosine in the chronically inflamed liver and the tumor microenvironment must be presumed, e.g., modulating effector functions of tumor infiltrating lymphocytes. Evidence of efficacy of combining immunotherapy with targeting the CD39-CD73-A2AR axis is increasing. Targeting different molecules that are involved in generating adenosine may indeed boost anti-tumoral immunity and block a potential mechanism of acquired resistance to immunotherapy. In the case of HCC, we still have little robust functional evidence detailing possible interactions between immune checkpoints and purinergic signaling pathways. Our current efforts are to better understand effects of adenosinergic signaling on complex tumor-immune cell interactions in HCC.