CMTM6, a potential immunotherapy target

J Cancer Res Clin Oncol. 2022 Jan;148(1):47-56. doi: 10.1007/s00432-021-03835-9. Epub 2021 Nov 16.

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.

Publication types

  • Review

MeSH terms

  • B7-H1 Antigen / metabolism*
  • Cell Membrane / metabolism*
  • Humans
  • Immunotherapy
  • Lysosomes / metabolism
  • MARVEL Domain-Containing Proteins / metabolism*
  • Myelin Proteins / metabolism*
  • Neoplasms / immunology*
  • Neoplasms / pathology*
  • Tumor Escape / immunology*
  • Tumor Microenvironment / immunology

Substances

  • B7-H1 Antigen
  • CD274 protein, human
  • CMTM6 protein, human
  • MARVEL Domain-Containing Proteins
  • Myelin Proteins