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Journal of Extracellular Vesicles

Journal of Extracellular Vesicles

IF: 15.5
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Extracellular vesicle-packaged lncRNA from cancer-associated fibroblasts promotes immune evasion by downregulating HLA-A in pancreatic cancer

Published:23 July 2024 DOI: PMID: 39041344
Hanming Yao, Chengzhi Huang, Jinmao Zou, Weiling Liang, Yue Zhao, Kege Yang, Ziyi Zhong, Shurui Zhou, Jiajia Li, Yaqing Li, Lishu Xu, Kaihong Huang, Guoda Lian

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is characterised by immune evasion that contribute to poor prognosis. Cancer-associated fibroblasts (CAFs) play a pivotal role in orchestrating the PDAC tumour microenvironment. We investigated the role of CAF-derived extracellular vesicle (EV)-packaged long non-coding RNAs (lncRNAs) in immune evasion and explored gene therapy using engineered EVs loading small interfering RNAs (siRNAs) as a potential therapeutic strategy. Our findings highlight the significance of EV-packaged lncRNA RP11-161H23.5 from CAF in promoting PDAC immune evasion by downregulating HLA-A expression, a key component of antigen presentation. Mechanistically, RP11-161H23.5 forms a complex with CNOT4, a subunit of the mRNA deadenylase CCR4-NOT complex, enhancing the degradation of HLA-A mRNA by shortening its poly(A) tail. This immune evasion mechanism compromises the anti-tumour immune response. To combat this, we propose an innovative approach utilising engineered EVs as natural and biocompatible nanocarriers for siRNA-based gene therapy and this strategy holds promise for enhancing the effectiveness of immunotherapy in PDAC. Overall, our study sheds light on the critical role of CAF-derived EV-packaged lncRNA RP11-161H23.5/CNOT4/HLA-A axis in PDAC immune evasion and presents a novel avenue for therapeutic intervention.

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D-Luciferin 2591-17-5 C11H8N2O3S2 439 suppliers $6.00-$3108.00
D-Luciferin 2591-17-5 C11H8N2O3S2 439 suppliers $6.00-$3108.00
D-Luciferin 2591-17-5 C11H8N2O3S2 439 suppliers $6.00-$3108.00
D-Luciferin 2591-17-5 C11H8N2O3S2 439 suppliers $6.00-$3108.00
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