中文版 | English
Title

Tumor PKC delta instigates immune exclusion in EGFR-mutated non-small cell lung cancer

Author
Corresponding AuthorLiang, Hai-Hai; Fan, Xing-Xing
Publication Years
2022-12-08
DOI
Source Title
ISSN
1741-7015
Volume20Issue:1
Abstract
BackgroundThe recruitment of a sufficient number of immune cells to induce an inflamed tumor microenvironment (TME) is a prerequisite for effective response to cancer immunotherapy. The immunological phenotypes in the TME of EGFR-mutated lung cancer were characterized as non-inflamed, for which immunotherapy is largely ineffective. MethodsGlobal proteomic and phosphoproteomic data from lung cancer tissues were analyzed aiming to map proteins related to non-inflamed TME. The ex vivo and in vivo studies were carried out to evaluate the anti-tumor effect. Proteomics was applied to identify the potential target and signaling pathways. CRISPR-Cas9 was used to knock out target genes. The changes of immune cells were monitored by flow cytometry. The correlation between PKC delta and PD-L1 was verified by clinical samples. ResultsWe proposed that PKC delta, a gatekeeper of immune homeostasis with kinase activity, is responsible for the un-inflamed phenotype in EGFR-mutated lung tumors. It promotes tumor progression by stimulating extracellular matrix (ECM) and PD-L1 expression which leads to immune exclusion and assists cancer cell escape from T cell surveillance. Ablation of PKC delta enhances the intratumoral penetration of T cells and suppresses the growth of tumors. Furthermore, blocking PKC delta significantly sensitizes the tumor to immune checkpoint blockade (ICB) therapy (alpha PD-1) in vitro and in vivo model. ConclusionsThese findings revealed that PKC delta is a critical switch to induce inflamed tumors and consequently enhances the efficacy of ICB therapy in EGFR-mutated lung cancer. This opens a new avenue for applying immunotherapy against recalcitrant tumors.
Keywords
URL[Source Record]
Indexed By
Language
English
SUSTech Authorship
Others
Funding Project
Dr. Neher's Biophysics Laboratory for Innovative Drug Discovery["0003/2018/A1","0058/2020/A2"] ; [001/2020/ALC]
WOS Research Area
General & Internal Medicine
WOS Subject
Medicine, General & Internal
WOS Accession No
WOS:000895935400003
Publisher
Data Source
Web of Science
Citation statistics
Cited Times [WOS]:0
Document TypeJournal Article
Identifierhttp://kc.sustech.edu.cn/handle/2SGJ60CL/420787
DepartmentDepartment of Chemistry
Affiliation
1.Macau Univ Sci & Technol, Dr Nehers Biophys Lab Innovat Drug Discovery, State Key Lab Qual Res Chinese Med, Macau, Peoples R China
2.Harvard Med Sch, Dept Cardiol, Boston, MA USA
3.Southern Univ Sci & Technol, Dept Chem, Shenzhen, Guangdong, Peoples R China
4.Sichuan Univ, State Key Lab Biotherapy, Chengdu, Peoples R China
5.Sichuan Univ, West China Hosp, Canc Ctr, West China Med Sch, Chengdu, Peoples R China
6.TianJin Med Univ, Gen Hosp, Tianjin, Peoples R China
7.Harbin Med Univ, Coll Pharm, Dept Pharmacol, Harbin, Heilongjiang, Peoples R China
Recommended Citation
GB/T 7714
Zuo, Yi-Han,Gao, Wei-Na,Xie, Ya-Jia,et al. Tumor PKC delta instigates immune exclusion in EGFR-mutated non-small cell lung cancer[J]. BMC Medicine,2022,20(1).
APA
Zuo, Yi-Han.,Gao, Wei-Na.,Xie, Ya-Jia.,Yang, Sheng-Yong.,Zhou, Jin-Tai.,...&Fan, Xing-Xing.(2022).Tumor PKC delta instigates immune exclusion in EGFR-mutated non-small cell lung cancer.BMC Medicine,20(1).
MLA
Zuo, Yi-Han,et al."Tumor PKC delta instigates immune exclusion in EGFR-mutated non-small cell lung cancer".BMC Medicine 20.1(2022).
Files in This Item:
There are no files associated with this item.
Related Services
Recommend this item
Bookmark
Usage statistics
Export to Endnote
Export to Excel
Export to Csv
Altmetrics Score
Google Scholar
Similar articles in Google Scholar
[Zuo, Yi-Han]'s Articles
[Gao, Wei-Na]'s Articles
[Xie, Ya-Jia]'s Articles
Baidu Scholar
Similar articles in Baidu Scholar
[Zuo, Yi-Han]'s Articles
[Gao, Wei-Na]'s Articles
[Xie, Ya-Jia]'s Articles
Bing Scholar
Similar articles in Bing Scholar
[Zuo, Yi-Han]'s Articles
[Gao, Wei-Na]'s Articles
[Xie, Ya-Jia]'s Articles
Terms of Use
No data!
Social Bookmark/Share
No comment.

Items in the repository are protected by copyright, with all rights reserved, unless otherwise indicated.