Epithelial to Mesenchymal Transition Regulates Surface PD-L1 via CMTM6 and CMTM7 Induction in Breast Cancer

Cancers

BrettG. Hollier¹  JeanPaul Thiery²  TuanZea Tan³  Christine Gilles⁴  Guy Berchem⁵  Bassam Janji⁵  Meriem Hasmim⁵  Audrey Lequeux⁵  KrisVan Moer⁵  Malina Xiao⁵  MuhammadZaeem Noman⁵ 

[1] Australian Prostate Cancer Research Centre-Queensland (APCRC-Q), School of Biomedical Sciences, Faculty of Health, Queensland University of Technology, Princess Alexandra Hospital, Translational Research Institute, Brisbane, QLD 4102, Australia;Bioland Laboratory, Guangzhou Regenerative Medicine and Health, Guangdong Laboratory, Guangzhou 510320, China;Cancer Science Institute of Singapore, National University of Singapore, Singapore 119077, Singapore;GIGA-Cancer, Laboratory of Tumor and Development Biology, University of Liège, 4000 Liège, Belgium;Tumor Immunotherapy and Microenvironment (TIME) Group, Department of Oncology, Luxembourg Institute of Health (LIH), Luxembourg City, L-1526 Strassen, Luxembourg;

关键词: breast cancer;    epithelial to mesenchymal transition;    snail1;    CMTM family;    immune checkpoints;   

DOI  :  10.3390/cancers13051165

来源: DOAJ

【 摘 要 】

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^Mes cells) increased both PD-L1 and CMTM6. CMTM6 silencing in MCF-7^Mes cells partially reduced cell surface expression of PD-L1, indicating that a proportion of the PD-L1 on the surface of MCF-7^Mes 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^Mes 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.

【 授权许可】

Unknown