Nature immunology, 2019-07, Vol.20 (7), p.835-851
- Hu, Qingsong
- Ye, Youqiong
- Chan, Li-Chuan
- Li, Yajuan
- Liang, Ke
- Lin, Aifu
- Egranov, Sergey D
- Zhang, Yaohua
- Xia, Weiya
- Gong, Jing
- Pan, Yinghong
- Chatterjee, Sujash S
- Yao, Jun
- Evans, Kurt W
- Nguyen, Tina K
- Park, Peter K
- Liu, Jiewei
- Coarfa, Cristian
- Donepudi, Sri Ramya
- Putluri, Vasanta
- Putluri, Nagireddy
- Sreekumar, Arun
- Ambati, Chandrashekar R
- Hawke, David H
- Marks, Jeffrey R
- Gunaratne, Preethi H
- Caudle, Abigail S
- Sahin, Aysegul A
- Hortobagyi, Gabriel N
- Meric-Bernstam, Funda
- Chen, Lieping
- Yu, Dihua
- Hung, Mien-Chie
- Curran, Michael A
- Han, Leng
- Lin, Chunru
- Yang, Liuqing
2019
Volltextzugriff (PDF)
Details
- Autor(en) / Beteiligte
- Hu, Qingsong
- Ye, Youqiong
- Chan, Li-Chuan
- Li, Yajuan
- Liang, Ke
- Lin, Aifu
- Egranov, Sergey D
- Zhang, Yaohua
- Xia, Weiya
- Gong, Jing
- Pan, Yinghong
- Chatterjee, Sujash S
- Yao, Jun
- Evans, Kurt W
- Nguyen, Tina K
- Park, Peter K
- Liu, Jiewei
- Coarfa, Cristian
- Donepudi, Sri Ramya
- Putluri, Vasanta
- Putluri, Nagireddy
- Sreekumar, Arun
- Ambati, Chandrashekar R
- Hawke, David H
- Marks, Jeffrey R
- Gunaratne, Preethi H
- Caudle, Abigail S
- Sahin, Aysegul A
- Hortobagyi, Gabriel N
- Meric-Bernstam, Funda
- Chen, Lieping
- Yu, Dihua
- Hung, Mien-Chie
- Curran, Michael A
- Han, Leng
- Lin, Chunru
- Yang, Liuqing
- Titel
- Oncogenic lncRNA downregulates cancer cell antigen presentation and intrinsic tumor suppression
- Ist Teil von
- Nature immunology, 2019-07, Vol.20 (7), p.835-851
- Ort / Verlag
- United States
- Erscheinungsjahr
- 2019
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- How tumor cells genetically lose antigenicity and evade immune checkpoints remains largely elusive. We report that tissue-specific expression of the human long noncoding RNA LINK-A in mouse mammary glands initiates metastatic mammary gland tumors, which phenotypically resemble human triple-negative breast cancer (TNBC). LINK-A expression facilitated crosstalk between phosphatidylinositol-(3,4,5)-trisphosphate and inhibitory G-protein-coupled receptor (GPCR) pathways, attenuating protein kinase A-mediated phosphorylation of the E3 ubiquitin ligase TRIM71. Consequently, LINK-A expression enhanced K48-polyubiquitination-mediated degradation of the antigen peptide-loading complex (PLC) and intrinsic tumor suppressors Rb and p53. Treatment with LINK-A locked nucleic acids or GPCR antagonists stabilized the PLC components, Rb and p53, and sensitized mammary gland tumors to immune checkpoint blockers. Patients with programmed ccll death protein-1(PD-1) blockade-resistant TNBC exhibited elevated LINK-A levels and downregulated PLC components. Hence we demonstrate lncRNA-dependent downregulation of antigenicity and intrinsic tumor suppression, which provides the basis for developing combinational immunotherapy treatment regimens and early TNBC prevention.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1529-2908eISSN: 1529-2916DOI: 10.1038/s41590-019-0400-7Titel-ID: cdi_pubmed_primary_31160797
- Format
- –
- Schlagworte
- Adenoma - genetics, Adenoma - metabolism, Animals, Antigen Presentation - immunology, Cell Line, Tumor, Cell Proliferation, Cell Transformation, Neoplastic - genetics, Cell Transformation, Neoplastic - metabolism, Cyclic AMP-Dependent Protein Kinases - metabolism, Disease Models, Animal, Disease Progression, Gene Expression Regulation, Neoplastic, Humans, Mice, Neoplasms - genetics, Neoplasms - immunology, Neoplasms - metabolism, Neoplasms - pathology, Oncogenes, Phosphorylation, Receptors, G-Protein-Coupled - antagonists & inhibitors, RNA, Long Noncoding - genetics, Tumor Escape - genetics, Tumor Escape - immunology, Tumor Microenvironment - genetics, Tumor Microenvironment - immunology, Tumor Suppressor Protein p53 - metabolism, Ubiquitination, Xenograft Model Antitumor Assays