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Biology and function of exosomes in tumor immunotherapy - 04/12/23

Doi : 10.1016/j.biopha.2023.115853 
Can Liu a, b, Cong Xia c, , Chenglai Xia a, b,
a Foshan Maternity and Chlid Healthcare Hospital, Foshan 528000, China 
b School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 515150, China 
c Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Dalian Medical University, Dalian 116023, China 

Corresponding author.⁎⁎Corresponding author at: Foshan Maternity and Chlid Healthcare Hospital, Foshan 528000, China.Foshan Maternity and Chlid Healthcare HospitalFoshan528000China.

Abstract

Exosomes are nano-scale extracellular vesicles that are found widely in various biological fluids. As messengers, exosomes deliver characteristic biological information from donor cells, facilitating their accumulation and subsequent transfer of information to tumor immune cells. Immunotherapy is a cutting-edge strategy for cancer therapy, but it has not yet reached its full potential owing to severe side effects and limited efficacy. Exosomes possess antigens and immunostimulatory molecules and can serve as cell-free vaccines to induce antitumor immunity. In addition, given their stability, low immunogenicity, and targeting ability, exosomes represent ideal drug delivery systems in tumor immunotherapy by delivering cargoes, including non-coding ribonucleic acids (RNAs), membrane proteins, chemotherapeutic agents, and immune cell death inducers. Exosomes can also be engineered to precisely target tumor cells. However, as a rising star in tumor immunotherapy, exosomes are also impeded by some challenges, including the lack of uniform technical standards for their isolation and purification, the need to improve exosomal cargo loading for efficient exosome delivery, and the expansion of clinical trials, which are currently in their infancy. Long-term, multi-center, and large-scale clinical trials are needed to evaluate the performance of exosomes in the future. Nonetheless, exosomes have demonstrated encouraging performance in tumor immunotherapy. In this review, we summarize the potential and challenges of exosomes in tumor immunotherapy, with the aim to shed light on exosomes as new-era tumor immunotherapy tools.

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Graphical Abstract




 : 

Role of exosomes in tumor immunotherapy. Engineered exosomes that express SIRPα, PD-1, and LILRB1 play a role similar to immune cells, interact with receptors (CD47, PD-L1, and B2M) on tumor cells, promote the phagocytosis of tumor cells, and enhance the presentation of antigen by immune cells. CD47 expressed on engineered exosomes mimics the “don’t-eat-me” signal and inhibits clearance by the immune system when exosomes serve as drug delivery systems, allowing for efficient uptake of exosomes by tumor cells. DEX and TEX are the two main candidates for exosomal tumor vaccines. TEXs transfer a variety of tumor-related antigens to DCs, which activate tumor-specific CTLs to induce antitumor immunity. DEXs deliver various molecules for antigen presentation and activation of immune cells.


Role of exosomes in tumor immunotherapy. Engineered exosomes that express SIRPα, PD-1, and LILRB1 play a role similar to immune cells, interact with receptors (CD47, PD-L1, and B2M) on tumor cells, promote the phagocytosis of tumor cells, and enhance the presentation of antigen by immune cells. CD47 expressed on engineered exosomes mimics the “don’t-eat-me” signal and inhibits clearance by the immune system when exosomes serve as drug delivery systems, allowing for efficient uptake of exosomes by tumor cells. DEX and TEX are the two main candidates for exosomal tumor vaccines. TEXs transfer a variety of tumor-related antigens to DCs, which activate tumor-specific CTLs to induce antitumor immunity. DEXs deliver various molecules for antigen presentation and activation of immune cells.ga1

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Abbreviations : ATP, B2M, CD, circRNA, CTL, DC, DEX, HMGB1, ICD, IFN, IL, LILRB1, lncRNA, miRNA, ncRNA, MHC, MSC, NK, PD-1, PD-L1, RGD, RNA, siRNA, SIRP, TGF-β, TEX

Keywords : Exosomes, Tumor immunotherapy, Tumor vaccine, Drug delivery system


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© 2023  The Authors. Publié par Elsevier Masson SAS. Tous droits réservés.
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