Journal article

CMTM6 maintains the expression of PD-L1 and regulates anti-tumour immunity

Marian L Burr, Christina E Sparbier, Yih-Chih Chan, James C Williamson, Katherine Woods, Paul A Beavis, Enid YN Lam, Melissa A Henderson, Charles C Bell, Sabine Stolzenburg, Omer Gilan, Stuart Bloor, Tahereh Noori, David W Morgens, Michael C Bassik, Paul J Neeson, Andreas Behren, Phillip K Darcy, Sarah-Jane Dawson, Ilia Voskoboinik Show all

NATURE | NATURE RESEARCH | Published : 2017

Abstract

Cancer cells exploit the expression of the programmed death-1 (PD-1) ligand 1 (PD-L1) to subvert T-cell-mediated immunosurveillance. The success of therapies that disrupt PD-L1-mediated tumour tolerance has highlighted the need to understand the molecular regulation of PD-L1 expression. Here we identify the uncharacterized protein CMTM6 as a critical regulator of PD-L1 in a broad range of cancer cells, by using a genome-wide CRISPR-Cas9 screen. CMTM6 is a ubiquitously expressed protein that binds PD-L1 and maintains its cell surface expression. CMTM6 is not required for PD-L1 maturation but co-localizes with PD-L1 at the plasma membrane and in recycling endosomes, where it prevents PD-L1 fro..

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Grants

Awarded by NHMRC


Awarded by Wellcome Trust PRF


Awarded by NATIONAL HUMAN GENOME RESEARCH INSTITUTE


Awarded by Cancer Research UK


Awarded by National Institute for Health Research


Awarded by National Breast Cancer Foundation


Funding Acknowledgements

M.L.B. is supported by a Cancer Research UK Fellowship, Addenbrooke's Charitable Trust award and NIHR fellowship. M.A.D. is supported by a Senior Leukaemia Foundation Australia Fellowship and work in the Dawson laboratory is supported by the NHMRC (Grants 1085015, 1106444 and 1106447) Cancer Council Victoria and Leukaemia Foundation Australia. P.J.L. is supported by a Wellcome Trust PRF (101835/Z/13/Z) and work in the Lehner laboratory is supported by NHSBT, NIHR Cambridge BRC, a Wellcome Trust Strategic Award to CIMR, and the Addenbrooke's Charitable Trust.