CKLF-like MARVEL transmembrane domain-containing protein 6 is a member of the chemokine-like factor-like MARVEL transmembrane domain-containing family. CMTM6 stabilizes plasma membrane expression of PD-L1, an immune inhibitory ligand critical for immune tolerance to self and anti-tumor immunity. CMTM6 associates with PD-L1 at recycling endosomes, where it protects PD-L1 from being targeted for lysosomal degradation by preventing STUB1-mediated PD-L1 ubiquitination. CMTM6 may stabilize PD-L1 expression on antigen presenting cells and potentiate inhibitory signaling by PD-1 on T cells, triggering T cell inhibition and exhaustion. CMTM6 has also been shown to interact with CD58, ARG1, ENO1, and TMPO. Due to the role of CMTM6 in regulating the immune system, it is being investigated as an immunotherapeutic target for the treatment of cancer.
[1] Han, W. et al. (2003) Genomics 81, 609-17.
[2] Burr, M.L. et al. (2017) Nature 549, 101-5.
[3] Mezzadra, R. et al. (2017) Nature 549, 106-10.
