CMTM6, a potential immunotherapy target

Abstract

The CKLF-like MARVEL transmembrane domain-containing protein 6 (CMTM6), which binds to the programmed death ligand 1 (PD-L1) and stabilizes the expression of PD-L1 on the cell surface, has been recently discovered as a novel regulator of PD-L1 expression in cancer. PD-L1 is an immune checkpoint inhibitory molecule that can mediate the immune escape of tumor cells in various tumors and has been studied intensively in recent years. In 2017, two articles simultaneously reported that CMTM6 can stabilize the expression of PD-L1 on the plasma membrane and prevent PD-L1 from being degraded by lysosomes; therefore, CMTM6 may play an important role in tumor cell immune escape and immunosuppression. At present, there are few studies on the relationship between the expression of CMTM6 and PD-L1 in different tumors and diseases. These studies together suggested that CMTM6 may be a potential novel immunotherapy target. In this review, we briefly describe the latest research progresses of CMTM6 in various cancers and other diseases.

Keywords: CMTM6; Immunotherapy; PD-L1.

Fig. 1

In CHB, ETV up-regulates the expression of PD-L1 by up-regulating CMTM6. In hepatocytes infected with hepatitis B virus, ETV affects the transfer of PD-L1 from the cytoplasm to the cell surface by up-regulating CMTM6, thereby up-regulating PD-L1 on the surface of hepatocytes

Fig. 2

CMTM6 regulates the expression of PD-L1 in cancer. CMTM6 maintains the expression of PD-L1 on the cell surface by inhibiting the degradation of PD-L1 in the lysosome. CMTM6 in exosomes secreted by OSCC cancer cells induces tumor-associated macrophages to polarize from M1 type to M2 type through the ERK1/2 pathway. In OSCC, CMTM6 can interact with membrane bound Enolase-1 and regulate Wnt signaling mediated by AKT /GSK3β axis to drive cisplatin resistance