Prospect of Extracellular Vesicles in Tumor Immunotherapy

Overview

Journal Front Immunol

Specialty Allergy & Immunology

Date 2025 Mar 13

PMID 40078996

Authors

Wenbo Xia

Yunhan Tan

Yongen Liu

Na Xie

Huili Zhu

Affiliations

Soon will be listed here.

Abstract

Extracellular vesicles (EVs), as cell-derived small vesicles, facilitate intercellular communication within the tumor microenvironment (TME) by transporting biomolecules. EVs from different sources have varied contents, demonstrating differentiated functions that can either promote or inhibit cancer progression. Thus, regulating the formation, secretion, and intake of EVs becomes a new strategy for cancer intervention. Advancements in EV isolation techniques have spurred interest in EV-based therapies, particularly for tumor immunotherapy. This review explores the multifaceted functions of EVs from various sources in tumor immunotherapy, highlighting their potential in cancer vaccines and adoptive cell therapy. Furthermore, we explore the potential of EVs as nanoparticle delivery systems in tumor immunotherapy. Finally, we discuss the current state of EVs in clinical settings and future directions, aiming to provide crucial information to advance the development and clinical application of EVs for cancer treatment.

References

Wang M, Altinoglu S, Takeda Y, Xu Q . Integrating Protein Engineering and Bioorthogonal Click Conjugation for Extracellular Vesicle Modulation and Intracellular Delivery. PLoS One. 2015; 10(11):e0141860. PMC: 4631329. DOI: 10.1371/journal.pone.0141860. View

Liu W, Li L, Rong Y, Qian D, Chen J, Zhou Z . Hypoxic mesenchymal stem cell-derived exosomes promote bone fracture healing by the transfer of miR-126. Acta Biomater. 2019; 103:196-212. DOI: 10.1016/j.actbio.2019.12.020. View

Li Y, Zhao W, Wang Y, Wang H, Liu S . Extracellular vesicle-mediated crosstalk between pancreatic cancer and stromal cells in the tumor microenvironment. J Nanobiotechnology. 2022; 20(1):208. PMC: 9063273. DOI: 10.1186/s12951-022-01382-0. View

Skog J, Wurdinger T, van Rijn S, Meijer D, Gainche L, Sena-Esteves M . Glioblastoma microvesicles transport RNA and proteins that promote tumour growth and provide diagnostic biomarkers. Nat Cell Biol. 2008; 10(12):1470-6. PMC: 3423894. DOI: 10.1038/ncb1800. View

Munich S, Sobo-Vujanovic A, Buchser W, Beer-Stolz D, Vujanovic N . Dendritic cell exosomes directly kill tumor cells and activate natural killer cells via TNF superfamily ligands. Oncoimmunology. 2012; 1(7):1074-1083. PMC: 3494621. DOI: 10.4161/onci.20897. View

Raghunathan R, Turajane K, Wong L . Biomarkers in Neurodegenerative Diseases: Proteomics Spotlight on ALS and Parkinson's Disease. Int J Mol Sci. 2022; 23(16). PMC: 9409485. DOI: 10.3390/ijms23169299. View

Timaner M, Letko-Khait N, Kotsofruk R, Benguigui M, Beyar-Katz O, Rachman-Tzemah C . Therapy-Educated Mesenchymal Stem Cells Enrich for Tumor-Initiating Cells. Cancer Res. 2018; 78(5):1253-1265. PMC: 5924870. DOI: 10.1158/0008-5472.CAN-17-1547. View

Hinshaw D, Shevde L . The Tumor Microenvironment Innately Modulates Cancer Progression. Cancer Res. 2019; 79(18):4557-4566. PMC: 6744958. DOI: 10.1158/0008-5472.CAN-18-3962. View

Qian F, Huang Z, Zhong H, Lei Q, Ai Y, Xie Z . Analysis and Biomedical Applications of Functional Cargo in Extracellular Vesicles. ACS Nano. 2022; 16(12):19980-20001. DOI: 10.1021/acsnano.2c11298. View

10.

Wei K, Zhang H, Yang S, Cui Y, Zhang B, Liu J . Chemo-drugs in cell microparticles reset antitumor activity of macrophages by activating lysosomal P450 and nuclear hnRNPA2B1. Signal Transduct Target Ther. 2023; 8(1):22. PMC: 9852455. DOI: 10.1038/s41392-022-01212-7. View

11.

Hu K, Li N, Li J, Chen Z, Wang J, Sheng L . Exosome circCMTM3 promotes angiogenesis and tumorigenesis of hepatocellular carcinoma through miR-3619-5p/SOX9. Hepatol Res. 2021; 51(11):1139-1152. DOI: 10.1111/hepr.13692. View

12.

Meliciano A, Salvador D, Mendonca P, Louro A, Serra M . Clinically Expired Platelet Concentrates as a Source of Extracellular Vesicles for Targeted Anti-Cancer Drug Delivery. Pharmaceutics. 2023; 15(3). PMC: 10056378. DOI: 10.3390/pharmaceutics15030953. View

13.

Cai Z, Yang F, Yu L, Yu Z, Jiang L, Wang Q . Activated T cell exosomes promote tumor invasion via Fas signaling pathway. J Immunol. 2012; 188(12):5954-61. DOI: 10.4049/jimmunol.1103466. View

14.

Chen Z, Yue Z, Yang K, Shen C, Cheng Z, Zhou X . Four Ounces Can Move a Thousand Pounds: The Enormous Value of Nanomaterials in Tumor Immunotherapy. Adv Healthc Mater. 2023; 12(26):e2300882. DOI: 10.1002/adhm.202300882. View

15.

Won S, Lee C, Bae S, Lee J, Choi D, Kim M . Mass-produced gram-negative bacterial outer membrane vesicles activate cancer antigen-specific stem-like CD8 T cells which enables an effective combination immunotherapy with anti-PD-1. J Extracell Vesicles. 2023; 12(8):e12357. PMC: 10415594. DOI: 10.1002/jev2.12357. View

16.

Taghikhani A, Farzaneh F, Sharifzad F, Mardpour S, Ebrahimi M, Hassan Z . Engineered Tumor-Derived Extracellular Vesicles: Potentials in Cancer Immunotherapy. Front Immunol. 2020; 11:221. PMC: 7069476. DOI: 10.3389/fimmu.2020.00221. View

17.

Zhang Z, Hu J, Ishihara M, Sharrow A, Flora K, He Y . The miRNA-21-5p Payload in Exosomes from M2 Macrophages Drives Tumor Cell Aggression via PTEN/Akt Signaling in Renal Cell Carcinoma. Int J Mol Sci. 2022; 23(6). PMC: 8949275. DOI: 10.3390/ijms23063005. View

18.

Hodgins J, Khan S, Park M, Auer R, Ardolino M . Killers 2.0: NK cell therapies at the forefront of cancer control. J Clin Invest. 2019; 129(9):3499-3510. PMC: 6715409. DOI: 10.1172/JCI129338. View

19.

Samara A, Anbar M, Shapira S, Zemlyansky A, Zozovsky A, Raanani P . Using natural killer cell-derived exosomes as a cell-free therapy for leukemia. Hematol Oncol. 2022; 41(3):487-498. DOI: 10.1002/hon.3111. View

20.

Lau C, Wong D . Breast cancer exosome-like microvesicles and salivary gland cells interplay alters salivary gland cell-derived exosome-like microvesicles in vitro. PLoS One. 2012; 7(3):e33037. PMC: 3308964. DOI: 10.1371/journal.pone.0033037. View