Asset Details
Do you wish to reserve the book?
STT3-dependent PD-L1 accumulation on cancer stem cells promotes immune evasion
Hey, we have placed the reservation for you!
By the way, why not check out events that you can attend while you pick your title.
Oops! Something went wrong.
Looks like we were not able to place the reservation. Kindly try again later.
Are you sure you want to remove the book from the shelf?
STT3-dependent PD-L1 accumulation on cancer stem cells promotes immune evasion
Do you wish to request the book?
STT3-dependent PD-L1 accumulation on cancer stem cells promotes immune evasion
Please be aware that the book you have requested cannot be checked out. If you would like to checkout this book, you can reserve another copy
We have requested the book for you!
Your request is successful and it will be processed during the Library working hours. Please check the status of your request in My Requests.
Oops! Something went wrong.
Looks like we were not able to place your request. Kindly try again later.
Journal Article
STT3-dependent PD-L1 accumulation on cancer stem cells promotes immune evasion
2018
Overview
Enriched PD-L1 expression in cancer stem-like cells (CSCs) contributes to CSC immune evasion. However, the mechanisms underlying PD-L1 enrichment in CSCs remain unclear. Here, we demonstrate that epithelial–mesenchymal transition (EMT) enriches PD-L1 in CSCs by the EMT/β-catenin/STT3/PD-L1 signaling axis, in which EMT transcriptionally induces N-glycosyltransferase STT3 through β-catenin, and subsequent STT3-dependent PD-L1 N-glycosylation stabilizes and upregulates PD-L1. The axis is also utilized by the general cancer cell population, but it has much more profound effect on CSCs as EMT induces more STT3 in CSCs than in non-CSCs. We further identify a non-canonical mesenchymal–epithelial transition (MET) activity of etoposide, which suppresses the EMT/β-catenin/STT3/PD-L1 axis through TOP2B degradation-dependent nuclear β-catenin reduction, leading to PD-L1 downregulation of CSCs and non-CSCs and sensitization of cancer cells to anti-Tim-3 therapy. Together, our results link MET to PD-L1 stabilization through glycosylation regulation and reveal it as a potential strategy to enhance cancer immunotherapy efficacy.
PD-L1 accumulates on cancer stem cells and favours immune evasion but the mechanism underlying this accumulation are unknown. Here the authors show that epithelial-mesenchymal transition induces glycosylation and stabilisation of PD-L1; antagonising this process renders cancer cells sensitive to anti-Tim3-therapy.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 14/19
/ 631/67
/ 82/29
/ 96/106
/ 96/35
/ Animals
/ Cancer
/ DNA Topoisomerases, Type II - genetics
/ DNA Topoisomerases, Type II - immunology
/ Epithelial-Mesenchymal Transition
/ Female
/ Gene Expression Regulation, Neoplastic
/ Humanities and Social Sciences
/ Humans
/ Membrane Proteins - genetics
/ Membrane Proteins - immunology
/ Neoplastic Stem Cells - cytology
/ Neoplastic Stem Cells - immunology
/ Poly-ADP-Ribose Binding Proteins - genetics
/ Poly-ADP-Ribose Binding Proteins - immunology
/ Science
