PD-L1 expression is regulated by both DNA methylation and NF-κB during EMT signaling in non-small cell lung carcinoma

被引：195

作者：

Asgarova, A. ^{[1
]}

Asgarov, K. ^{[1
]}

Godet, Y. ^{[1
,2
]}

Peixoto, P. ^{[1
,8
]}

Nadaradjane, A. ^{[4
,5
,6
,7
]}

Boyer-Guittaut, M. ^{[1
]}

Galaine, J. ^{[1
]}

Guenat, D. ^{[1
]}

Mougey, V. ^{[1
]}

Perrard, J. ^{[1
]}

Pallandre, J. R. ^{[1
]}

Bouard, A. ^{[1
]}

Balland, J. ^{[1
]}

Tirole, C. ^{[1
]}

Adotevi, O. ^{[1
,2
]}

Hendrick, E. ^{[1
]}

Herfs, M. ^{[9
]}

Cartron, P. F. ^{[4
,5
,6
,7
]}

Borg, C. ^{[1
,2
,3
]}

Hervouet, E. ^{[1
,8
]}

机构：

[1] Univ Bourgogne Franche Comte, INSERM, Interact Hote Greffon Tumeur Ingn Cellulaire & Ge, EFS BFC,UMR1098, F-25000 Besancon, France

[2] Univ Hosp Besancon, Med Oncol Dept, Besancon, France

[3] Clin Invest Ctr Biotherapy 1431, Besancon, France

[4] Univ Nantes, INSERM, Unit S1232, Nantes, France

[5] Inst Cancerol Ouest, Nantes, France

[6] REpiCGO Canceropole Grand Ouest, Brest, France

[7] EpiSAVMEN, Reg Pays Loire, Brest, France

[8] EPIGENExp EPIgenet & GENe EXPress Tech Platform, Besancon, France

[9] Univ Liege, GIGA Canc, Lab Expt Pathol, Liege, Belgium

来源：

ONCOIMMUNOLOGY | 2018年 / 7卷 / 05期

关键词：

death receptors; DNA methylation; epithelial-mesenchymal transition; lung cancer; cancer; NF-kappa B; PD-L1; EPITHELIAL-MESENCHYMAL TRANSITION; CANCER; TUMOR; METASTASIS; BLOCKADE; NKG2D; SUPPLEMENTATION; NETWORKS; LIGANDS;

D O I：

10.1080/2162402X.2017.1423170

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

Tumor cells, which undergo Epithelial-mesenchymal transition (EMT) acquire increased capacities of proliferation, invasion and have the ability to generate metastases by escaping the immune system during their systemic migration. To escape the immune system, cancer cells may induce tolerance or resist elimination by immune effectors via multiple mechanisms and we hypothesized that EMT may control the expression of immune checkpoint inhibitors, then promoting immune evasion. PD-L1 (programmed cell death ligand 1) but not PD-L2 nor Galectin 9 or Death receptor (DR4, DR5 and Fas) and ligands (FasL and TRAIL) expression was up-regulated during cytokine-driven EMT in a reversible manner. Moreover PD-L1 is overexpressed in VIMENTIN positive NSCLC tissues. We also demonstrated that the expression of PD-L1 required both TNF alpha and TGF beta 1. Indeed, TGF beta 1 decreased DNMT1 content and that resulted in PD-L1 promoter demethylation whereas TNF alpha induced the NF-kappa B pathway that promoted expression of demethylated PD-L1 promoter.

引用

页数：13

共 55 条

[1]

Epithelial-to-Mesenchymal Transition and Autophagy Induction in Breast Carcinoma Promote Escape from T-cell-Mediated Lysis [J].

Akalay, Intissar ;

Janji, Bassam ;

Hasmim, Meriem ;

Noman, Muhammad Zaeem ;

Andre, Fabrice ;

De Cremoux, Patricia ;

Bertheau, Philippe ;

Badoual, Cecile ;

Vielh, Philippe ;

Larsen, Annette K. ;

Sabbah, Michele ;

Tan, Tuan Zea ;

Keira, Joan Herr ;

Hung, Nicole Tsang Ying ;

Thiery, Jean Paul ;

Mami-Chouaib, Fathia ;

Chouaib, Salem .

CANCER RESEARCH, 2013, 73 (08) :2418-2427

[2]

Checkpoint inhibitors in melanoma and early phase development in solid tumors: what's the future? [J].

Ascierto, Paolo A. ;

McArthur, Grant A. .

JOURNAL OF TRANSLATIONAL MEDICINE, 2017, 15

[3]

CMTM6 maintains the expression of PD-L1 and regulates anti-tumour immunity [J].

Burr, Marian L. ;

Sparbier, Christina E. ;

Chan, Yih-Chih ;

Williamson, James C. ;

Woods, Katherine ;

Beavis, Paul A. ;

Lam, Enid Y. N. ;

Henderson, Melissa A. ;

Bell, Charles C. ;

Stolzenburg, Sabine ;

Gilan, Omer ;

Bloor, Stuart ;

Noori, Tahereh ;

Morgens, David W. ;

Bassik, Michael C. ;

Neeson, Paul J. ;

Behren, Andreas ;

Darcy, Phillip K. ;

Dawson, Sarah-Jane ;

Voskoboinik, Ilia ;

Trapani, Joseph A. ;

Cebon, Jonathan ;

Lehner, Paul J. ;

Dawson, Mark A. .

NATURE, 2017, 549 (7670) :101-105

[4]

TGF-β induces global changes in DNA methylation during the epithelial-to-mesenchymal transition in ovarian cancer cells [J].

Cardenas, Horacio ;

Vieth, Edyta ;

Lee, Jiyoon ;

Segar, Mathew ;

Liu, Yunlong ;

Nephew, Kenneth P. ;

Matei, Daniela .

EPIGENETICS, 2014, 9 (11) :1461-1472

[5]

Involvement of DNMT 3B promotes epithelial-mesenchymal transition and gene expression profile of invasive head and neck squamous cell carcinomas cell lines [J].

Chen, Li-Hsuen ;

Hsu, Wen-Lin ;

Tseng, Yen-Ju ;

Liu, Dai-Wei ;

Weng, Ching-Feng .

BMC CANCER, 2016, 16

[6]

Metastasis is regulated via microRNA-200/ZEB1 axis control of tumour cell PD-L1 expression and intratumoral immunosuppression [J].

Chen, Limo ;

Gibbons, Don L. ;

Goswami, Sangeeta ;

Cortez, Maria Angelica ;

Ahn, Young-Ho ;

Byers, Lauren A. ;

Zhang, Xuejun ;

Yi, Xiaohui ;

Dwyer, David ;

Lin, Wei ;

Diao, Lixia ;

Wang, Jing ;

Roybal, Jonathon D. ;

Patel, Mayuri ;

Ungewiss, Christin ;

Peng, David ;

Antonia, Scott ;

Mediavilla-Varela, Melanie ;

Robertson, Gordon ;

Jones, Steve ;

Suraokar, Milind ;

Welsh, James W. ;

Erez, Baruch ;

Wistuba, Ignacio I. ;

Chen, Lieping ;

Peng, Di ;

Wang, Shanshan ;

Ullrich, Stephen E. ;

Heymach, John V. ;

Kurie, Jonathan M. ;

Qin, F. Xiao-Feng .

NATURE COMMUNICATIONS, 2014, 5

[7]

Chen YB, 2012, TUMORI, V98, P751, DOI 10.1700/1217.13499

[8]

A shed NKG2D ligand that promotes natural killer cell activation and tumor rejection [J].

Deng, Weiwen ;

Gowen, Benjamin G. ;

Zhang, Li ;

Wang, Lin ;

Lau, Stephanie ;

Iannello, Alexandre ;

Xu, Jianfeng ;

Rovis, Tihana L. ;

Xiong, Na ;

Raulet, David H. .

SCIENCE, 2015, 348 (6230) :136-139

[9]

Rae1 and H60 ligands of the NKG2D receptor stimulate tumour immunity [J].

Diefenbach, A ;

Jensen, ER ;

Jamieson, AM ;

Raulet, DH .

NATURE, 2001, 413 (6852) :165-171

[10]

Dong HD, 1999, NAT MED, V5, P1365

← 1 2 3 4 5 6 →