From the, Division of Immunology and Allergy, Department of Medicine, Karolinska Institutet, Solna, Sweden.
Department of Clinical Immunology and Transfusion Medicine, Karolinska University Hospital, Stockholm, Sweden.
J Intern Med. 2021 Feb;289(2):138-146. doi: 10.1111/joim.12963. Epub 2019 Aug 29.
Extracellular vesicles, especially exosomes, have been explored for cancer immunotherapy. The initial studies made use of autologous B-cell or dendritic cell-derived exosomes, with the idea that MHC-peptide complexes on the exosomal surface would stimulate an MHC-restricted cancer-specific immune response. This was also verified in mouse systems, whilst the effects in human clinical systems were more modest. Several studies have explored the mechanisms for exosomal T-cell activation, and a picture emerges where the antigen-presenting cells, possibly both B cells and dendritic cells of the recipient, are needed to induce a potent T-cell response to exosomes. Therefore, the exosomes function more as an adjuvant-like delivery system of antigens, and we need to further understand the exact components that trigger the most broad and potent immune responses. Here, we describe the grounds for using allogeneic exosomes for cancer therapy, something that would greatly improve the feasibility of new exosome-based immunotherapeutic approaches to cure cancer.
细胞外囊泡，特别是外泌体，已被探索用于癌症免疫治疗。最初的研究利用了自体 B 细胞或树突状细胞来源的外泌体，其理念是外泌体表面的 MHC-肽复合物将刺激 MHC 受限的癌症特异性免疫反应。这在小鼠系统中得到了验证，而在人类临床系统中的效果则更为温和。一些研究探索了外泌体 T 细胞激活的机制，一幅图景浮现出来，即供体的抗原呈递细胞（可能包括 B 细胞和树突状细胞）需要诱导对外泌体的强烈 T 细胞反应。因此，外泌体更像是一种类似佐剂的抗原传递系统，我们需要进一步了解触发最广泛和最强免疫反应的确切成分。在这里，我们描述了使用同种异体外泌体进行癌症治疗的理由，这将极大地提高基于外泌体的新型免疫治疗方法治愈癌症的可行性。
