Please use this identifier to cite or link to this item:
https://ahro.austin.org.au/austinjspui/handle/1/17408
Full metadata record
DC Field | Value | Language |
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dc.contributor.author | Burr, Marian L | - |
dc.contributor.author | Sparbier, Christina E | - |
dc.contributor.author | Chan, Yih-Chih | - |
dc.contributor.author | Williamson, James C | - |
dc.contributor.author | Woods, Katherine | - |
dc.contributor.author | Beavis, Paul A | - |
dc.contributor.author | Lam, Enid Y N | - |
dc.contributor.author | Henderson, Melissa A | - |
dc.contributor.author | Bell, Charles C | - |
dc.contributor.author | Stolzenburg, Sabine | - |
dc.contributor.author | Gilan, Omer | - |
dc.contributor.author | Bloor, Stuart | - |
dc.contributor.author | Noori, Tahereh | - |
dc.contributor.author | Morgens, David W | - |
dc.contributor.author | Bassik, Michael C | - |
dc.contributor.author | Neeson, Paul J | - |
dc.contributor.author | Behren, Andreas | - |
dc.contributor.author | Darcy, Phillip K | - |
dc.contributor.author | Dawson, Sarah-Jane | - |
dc.contributor.author | Voskoboinik, Ilia | - |
dc.contributor.author | Trapani, Joseph A | - |
dc.contributor.author | Cebon, Jonathan S | - |
dc.contributor.author | Lehner, Paul J | - |
dc.contributor.author | Dawson, Mark A | - |
dc.date | 2017 | - |
dc.date.accessioned | 2018-04-11T01:10:43Z | - |
dc.date.available | 2018-04-11T01:10:43Z | - |
dc.date.issued | 2017 | - |
dc.identifier.citation | Nature 2017; 549(7670): 101-105 | - |
dc.identifier.uri | https://ahro.austin.org.au/austinjspui/handle/1/17408 | - |
dc.description.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 from being targeted for lysosome-mediated degradation. Using a quantitative approach to profile the entire plasma membrane proteome, we find that CMTM6 displays specificity for PD-L1. Notably, CMTM6 depletion decreases PD-L1 without compromising cell surface expression of MHC class I. CMTM6 depletion, via the reduction of PD-L1, significantly alleviates the suppression of tumour-specific T cell activity in vitro and in vivo. These findings provide insights into the biology of PD-L1 regulation, identify a previously unrecognized master regulator of this critical immune checkpoint and highlight a potential therapeutic target to overcome immune evasion by tumour cells. | - |
dc.language.iso | eng | - |
dc.title | CMTM6 maintains the expression of PD-L1 and regulates anti-tumour immunity. | - |
dc.type | Journal Article | - |
dc.identifier.journaltitle | Nature | - |
dc.identifier.affiliation | Cancer Research Division, Peter MacCallum Cancer Centre, Melbourne, Victoria 3000, Australia | - |
dc.identifier.affiliation | Sir Peter MacCallum Department of Oncology, University of Melbourne, Victoria 3052, Australia | - |
dc.identifier.affiliation | Cambridge Institute for Medical Research, Cambridge Biomedical Campus, Hills Road, Cambridge CB2 0XY, UK | - |
dc.identifier.affiliation | School of Cancer Medicine, La Trobe University, Melbourne, Victoria 3086, Australia | - |
dc.identifier.affiliation | Olivia Newton-John Cancer Research Institute, Heidelberg, Victoria, Australia | - |
dc.identifier.affiliation | Department of Genetics, Stanford University, Stanford, California, USA | - |
dc.identifier.affiliation | Centre for Cancer Research, University of Melbourne, Melbourne, Australia | - |
dc.identifier.doi | 10.1038/nature23643 | - |
dc.identifier.pubmedid | 28813417 | - |
dc.type.austin | Journal Article | - |
dc.type.austin | Research Support, Non-U.S. Gov't | - |
local.name.researcher | Cebon, Jonathan S | |
item.openairetype | Journal Article | - |
item.openairecristype | http://purl.org/coar/resource_type/c_18cf | - |
item.languageiso639-1 | en | - |
item.grantfulltext | none | - |
item.cerifentitytype | Publications | - |
item.fulltext | No Fulltext | - |
crisitem.author.dept | Olivia Newton-John Cancer Research Institute | - |
Appears in Collections: | Journal articles |
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