The A2A adenosine receptor (A2AAR) plays critical roles in human physiology and pathophysiology, which makes it an important drug target. Previous drug-discovery efforts targeting the A2AAR have been focused on the use of A2AAR antagonists for the treatment of Parkinson’s disease. More recently, the A2AAR has attracted additional attention for its roles in immuno-oncology, and a number of A2AAR antagonists are currently used as lead compounds for antitumor drugs in both preclinical models and clinical trials. This review surveys recent advances in the development of A2AAR antagonists for cancer immunotherapy. The therapeutic potential of representative A2AAR antagonists is discussed based on both animal efficacy studies and clinical data.

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Histone deacetylase (HDAC) is an epigenetic antitumor drug target, but most existing HDAC inhibitors show limited antitumor activity and their use is often accompanied by serious adverse effects. To overcome these problems, we designed and synthesized a series of triazole-containing compounds as novel HDAC inhibitors. Among them, compound 19h exhibited potent and selective inhibition of HDAC1, with good antiproliferative activity in vitro and an excellent pharmacokinetic profile. Compound 19h significantly inhibited the growth of human tumor xenografts in nude mice and murine tumor growth in immune-competent mice bearing MC38 colon cancer. In the MC38 model, 19h increased the ratio of splenic CD4 + T effector cells and promoted complete tumor regression in 5/6 animals when combined with the mPD-1 antibody. These results suggested that selective class I HDAC inhibitors exert direct tumor growth inhibition and indirect immune cellmediated antitumor effects and are synergistic with immune checkpoint inhibitors.