Novel regulators of PD-L1 expression in cancer: CMTM6 and CMTM4—a new avenue to enhance the therapeutic benefits of immune checkpoint inhibitors

During the past several decades, the efforts of cancer immunotherapy have been focused on identifying specific tumor antigens to augment antitumor immunity. However, this approach has been constantly challenged by the complexity and diversity of gene mutations and protein modification present in human cancers as well a complex tumor microenvironment, resulting in limited or failed therapeutic success (1-3). Recently discovered immune checkpoint pathways, including programmed death receptor 1/programmed death ligand 1 (PD-1/PD-L1) signaling pathway, were shown to protect host from overactive T-effector cells not only in cancer but also during microbial infections (4,5).