CD112R is a coinhibitory receptor belonging to the poliovirus receptor (PVR) family, originally known as the PVR-associated Ig domain (PVRIG). Human CD112R is a 36kD single transmembrane protein containing a transmembrane region, a long intracellular domain, and an extracellular immunoglobulin variant (IgV)

domain. CD112R (PVRIG) is commonly expressed on natural killer (NK) and T cells. It binds to a ligand (CD112 or PVRL2/nectin-2) and inhibits the strength of T and NK cell responses to tumor cells. Therefore, CD112R is considered as a novel immune checkpoint with high potential in tumor immunotherapy. High levels

of CD112 expression are associated with tumor progression and poor prognosis in most cancer patients. Currently, inhibitors of CD112R have been validated in clinical trials in cancer patients, and CD112R may be a very promising target. Clinical results suggest that CD112R blocker can not only be used as an adjuvant

therapy, but also may be a feasible alternative to individual therapy. With the in-depth research on the regulation of CD112R/ CD112-mediated immune response, it will help to design the optimal combination strategy of CD112R blocking agents for cancer patients, and bring benefits to more cancer patients.