Small extracellular vesicle miRNAs as biomarkers for predicting antitumor efficacy in lung adenocarcinoma treated with chemotherapy and checkpoint blockade

Small extracellular vesicle miRNAs as biomarkers for predicting antitumor efficacy in lung adenocarcinoma treated with chemotherapy and checkpoint blockade

Checkpoint blockade combined with chemotherapy has become an important treatment option for lung cancer patients in clinical settings. However, biomarkers that effectively identify true responders remain lacking. We assessed the potential of plasma small extracellular vesicle (sEV)-derived microRNAs...

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Main Authors: Si Sun, Fuchuang Zhang, Jiyang Zhang, Hui Yu, Zhihuang Hu, Xiaoya Xu, Xinmin Zhao, Sheng Chen, Yao Zhang, Baoning Nian, Ying Lin, Zhikuan Li, Zhenhua Wu, Bo Yu, Xianghua Wu, Huijie Wang, Xiaohua Hui, Dadong Zhang, Jialei Wang
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-03-01
Series:Frontiers in Immunology
Subjects:
sEVs
miRNA
immune checkpoint inhibitors
chemotherapy
lung cancer. sEV miRNAs predicting immunochemotherapy efficacy
Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2025.1573043/full
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Summary:Checkpoint blockade combined with chemotherapy has become an important treatment option for lung cancer patients in clinical settings. However, biomarkers that effectively identify true responders remain lacking. We assessed the potential of plasma small extracellular vesicle (sEV)-derived microRNAs (miRNAs) as biomarkers for predicting and identifying responders to combined immunochemotherapy. A total of 29 patients with lung adenocarcinoma who received pembrolizumab combined with pemetrexed and carboplatin were enrolled. The efficacy evaluation revealed that 24 patients obtained durable clinical benefits from combined immunochemotherapy, and the rest experienced disease progression. Using unsupervised hierarchical clustering, 56 differentially expressed miRNAs (DEMs) were identified between responders and nonresponders. Efficacy prediction models incorporating a combination of sEV miRNAs were established and showed good performance (area under the curve (AUC) > 0.9). In addition, we found that miR-96-5p and miR-6815-5p were notably downregulated in the nonresponder group, while miR-99b-3p, miR-100-5p, miR-193a-5p, and miR-320d were upregulated. These findings were further confirmed by clinical imaging. sEV miRNAs derived from patients with lung cancer showed promise for identifying true responders to combined immunochemotherapy.
ISSN:1664-3224

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