Updates on the Importance of CD200:CD200R Checkpoint Blockade in Solid Tumors and B cell Malignancies

Abstract

The last several years have seen the introduction into clinical medicine of a family of reagents directed towards so-called “checkpoint inhibitors”, which act at gateways in a developing immune response to regulate unwanted and/or harmful self-directed activation responses. The molecules involved at such gateways generally belong to an extended immunoglobulin supergene family, and contribute inhibitory signals to dampen over-exuberant responses. They include, but are not limited to, molecules of the CD28/cytotoxic T-lymphocyte antigen-4 (CTLA-4):B7.1/B7.2 receptor/ligand family; PD-1 and PDL-1; CD200 and CD200R; TIGIT and VISTA and their respective ligands (VSIG-3/IGSF11, Nectin), all of which are presumed to play a physiological role in maintaining natural self-tolerance. In the field of cancer immunotherapy, where the ultimate clinical goal is to improve immuno-targeting of cancer cells, triggering these checkpoint inhibitory signaling pathways, has the potential to thwart effective tumor immunity. This in turn has led to the characterization and application of multiple reagents, including antibodies and other designed inhibitory molecules, which can act as checkpoint blockade agents. Such reagents have had a dramatic effect on human cancer treatment, with marked success for anti-CTLA-4 and PD-1 in particular in clinical trials. This review elaborates on the promise on other more under-appreciated target molecules for checkpoint blockade in human B cell malignancies and solid tumors, particularly CD200:CD200R, and describes both the background, and newer studies, which highlight the potential importance of targeting the CD200:CD200R dyad in cancer immunobiology/therapy.