Insights into extracellular vesicles: From biogenesis and tumor immune modulation to their clinical potential in immunotherapy.
4 affiliations
- 1School of Information Science and Engineering, Shenyang Ligong University, Shenyang 110159, China.
- 2School of Mathematics and Statistics, Liaoning University, Shenyang 110036, China.
- 3Department of Anesthesiology, Shanxi Province Cancer Hospital/Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University, Taiyuan, China.
- 4Department of Anesthesiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
Abstract
Extracellular vesicles (EVs) constitute a key mode of intercellular communication that remodels the complex tumor immune microenvironment by delivering diverse bioactive cargoes between tumor and immune cells. Nucleic acid species, encompassing microRNAs (miRNAs), messenger RNA (mRNAs), and other RNA transcripts, are functionally potent EV cargoes whose selective packaging dictates downstream immune signaling output. This review describes the molecular mechanisms driving selective RNA sorting into EVs, emphasizing sequence-motif recognition and core RNA-binding proteins FMR1 and TRIM25, which govern the enrichment of distinct RNA populations. We illustrate how EV-shuttled RNA molecules elicit context-dependent functional changes across regulatory T cells, myeloid-derived suppressor cells, and macrophages to shape antitumor or pro-tumor immune states. It critically integrates liquid biopsy evidence for EV-borne RNAs and EV-associated programmed death-ligand 1 (PD-L1) as predictive biomarkers of immunotherapy response in melanoma, non-small cell lung cancer, and hepatocellular carcinoma and dissects technical confounders such as non-vesicular RNA contamination and inconsistent isolation protocols. This review further compares nucleic acid loading strategies for native EVs versus cell-membrane-mimetic nanovesicles and explores their applicability for mRNA-based nanovaccines and combinatorial immunotherapy. We highlight underappreciated translational obstacles, noting that harmonized analytical standards, strict encapsulated cargo validation, and independent prospective multicenter trials are essential to translate EV-nucleic acid signatures into personalized cancer immunotherapy.
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BibTeX
@article{ma2026insights,
title = {{Insights into extracellular vesicles: From biogenesis and tumor immune modulation to their clinical potential in immunotherapy.}},
author = {Shuang Ma and Aoyan Qi and Jiaxuan Wu and Yue Niu and Wanying Xu and Xiaolin Wu and Yi Liu and Tao Yan},
journal = {Molecular therapy. Nucleic acids},
year = {2026},
month = sep,
doi = {10.1016/j.omtn.2026.103116},
url = {https://europepmc.org/article/MED/42909369},
note = {CC BY},
}
RIS
TY - JOUR
TI - Insights into extracellular vesicles: From biogenesis and tumor immune modulation to their clinical potential in immunotherapy.
AU - Shuang Ma
AU - Aoyan Qi
AU - Jiaxuan Wu
AU - Yue Niu
AU - Wanying Xu
AU - Xiaolin Wu
AU - Yi Liu
AU - Tao Yan
PY - 2026
DA - 2026/09/26
JO - Molecular therapy. Nucleic acids
DO - 10.1016/j.omtn.2026.103116
UR - https://europepmc.org/article/MED/42909369
AB - Extracellular vesicles (EVs) constitute a key mode of intercellular communication that remodels the complex tumor immune microenvironment by delivering diverse bioactive cargoes between tumor and immune cells. Nucleic acid species, encompassing microRNAs (miRNAs), messenger RNA (mRNAs), and other RNA transcripts, are functionally potent EV cargoes whose selective packaging dictates downstream immune signaling output. This review describes the molecular mechanisms driving selective RNA sorting into EVs, emphasizing sequence-motif recognition and core RNA-binding proteins FMR1 and TRIM25, which govern the enrichment of distinct RNA populations. We illustrate how EV-shuttled RNA molecules elicit context-dependent functional changes across regulatory T cells, myeloid-derived suppressor cells, and macrophages to shape antitumor or pro-tumor immune states. It critically integrates liquid biopsy evidence for EV-borne RNAs and EV-associated programmed death-ligand 1 (PD-L1) as predictive biomarkers of immunotherapy response in melanoma, non-small cell lung cancer, and hepatocellular carcinoma and dissects technical confounders such as non-vesicular RNA contamination and inconsistent isolation protocols. This review further compares nucleic acid loading strategies for native EVs versus cell-membrane-mimetic nanovesicles and explores their applicability for mRNA-based nanovaccines and combinatorial immunotherapy. We highlight underappreciated translational obstacles, noting that harmonized analytical standards, strict encapsulated cargo validation, and independent prospective multicenter trials are essential to translate EV-nucleic acid signatures into personalized cancer immunotherapy.
SN - 2162-2531
ER -