Tumor Immunotherapy and Microenvironment (TIME) Group, Department of Oncology, Luxembourg Institute of Health (LIH), Luxembourg City, L-1526 Strassen, Luxembourg.
Published: March 2021
AI Article Synopsis
Article Abstract
CMTM6 is a critical regulator of cell surface expression of PD-L1 in tumor cells, but little is known about the transcriptional regulation of CMTM6. Here we report that the expression of CMTM6 positively correlates with the epithelial to mesenchymal transition (EMT) score in breast cancer cell lines and with the major EMT marker Vimentin in triple-negative breast cancers (TNBC). We showed that CMTM6 is concomitantly overexpressed with PD-L1 in breast mesenchymal compared with the epithelial cells. Driving a mesenchymal phenotype in SNAI1-inducible MCF-7 cells (MCF-7 cells) increased both PD-L1 and CMTM6. CMTM6 silencing in MCF-7 cells partially reduced cell surface expression of PD-L1, indicating that a proportion of the PD-L1 on the surface of MCF-7 cells depends on CMTM6. We also found a positive correlation between CMTM3 and CMTM7 expression with EMT score in breast cancer cells, and with Vimentin in TNBC patients. Dual knockdown of CMTM6 and CMTM7 significantly decreased PD-L1 surface expression in MCF-7 cells, indicating that both CMTM6 and CMTM7 regulate the expression of PD-L1. This study highlights the importance of CMTM6 and CMTM7 in EMT-induced PD-L1 and suggests that EMT, CMTM6 or CMTM7 modulators can be combined with anti-PD-L1 in patients with highly aggressive breast cancer.
The Chemokine-like factor ()-like MARVEL transmembrane domain-containing () family, comprising nine members, is involved in the tumorigenesis and progression of various cancers. However, the expression profiles and clinical significance of family members in hepatocellular carcinoma (HCC) are not fully clarified. In this study, the RNA-sequencing and clinical data were downloaded from The Cancer Genome Atlas (TCGA) databases.
Programmed death-ligand 1 (PD-L1) expression has long been used as a biomarker to stratify patients with cancer who will benefit from anti-PD-1/PD-L1 immunotherapy. However, the use of PD-L1 as a biomarker to guide treatment decisions has recently been called into question due to its dynamic and heterogeneous expression within each tumor and among different tumors as well as during tumor cell plasticity. Therefore, understanding the molecular basis of PD-L1 expression would enable delineating its value as a reliable biomarker in the clinic.
Antiphospholipid syndrome (APS) is a systemic autoimmune disease defined by thrombotic or obstetrical events and persistent antiphospholipid antibodies (aPLs). Chemokine-like factor-like MARVEL transmembrane domain-containing family (CMTM) is widely expressed in the immune system and may closely related to APS. This review aimed to systematically summarize the possible effects of CMTM on APS.
Tumor Immunotherapy and Microenvironment (TIME) Group, Department of Oncology, Luxembourg Institute of Health (LIH), Luxembourg City, L-1526 Strassen, Luxembourg.
CMTM6 is a critical regulator of cell surface expression of PD-L1 in tumor cells, but little is known about the transcriptional regulation of CMTM6. Here we report that the expression of CMTM6 positively correlates with the epithelial to mesenchymal transition (EMT) score in breast cancer cell lines and with the major EMT marker Vimentin in triple-negative breast cancers (TNBC). We showed that CMTM6 is concomitantly overexpressed with PD-L1 in breast mesenchymal compared with the epithelial cells.
Background: The CKLF-like MARVEL transmembrane domain-containing family (CMTM) is the protein product of at least one splice variant of each gene contained a Marvel (MAL and related proteins for vesicle trafficking and membrane link) domain, involved in a variety of cellular processes and the pathogenesis of diseases, including tumorigenesis. However, the diverse expression patterns and prognostic values of eight CMTMs have yet to be elucidated.
Objective: We analyzed the expressions and impacts on survival of different CMTM factors in BC patients to determine their potential diagnosis and prognosis values in BC.
