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警报素修饰的外泌体在小鼠大型已建立的肿瘤中引发持久的抗肿瘤免疫。

Alarmin-painted exosomes elicit persistent antitumor immunity in large established tumors in mice.

机构信息

Key Laboratory of Immune Microenvironment and Disease (Ministry of Education) & Tianjin Key Laboratory of Cellular Homeostasis and Human Diseases & Department of Cell Biology, Tianjin Medical University, Qixiangtai Road, Heping District, Tianjin, 300070, China.

Department of Hepatobiliary, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, 300060, China.

出版信息

Nat Commun. 2020 Apr 14;11(1):1790. doi: 10.1038/s41467-020-15569-2.

DOI:10.1038/s41467-020-15569-2
PMID:32286296
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7156382/
Abstract

Treating large established tumors is challenging for dendritic cell (DC)-based immunotherapy. DC activation with tumor cell-derived exosomes (TEXs) carrying multiple tumor-associated antigen can enhance tumor recognition. Adding a potent adjuvant, high mobility group nucleosome-binding protein 1 (HMGN1), boosts DCs' ability to activate T cells and improves vaccine efficiency. Here, we demonstrate that TEXs painted with the functional domain of HMGN1 (TEX-N1ND) via an exosomal anchor peptide potentiates DC immunogenicity. TEX-N1ND pulsed DCs (DC) elicit long-lasting antitumor immunity and tumor suppression in different syngeneic mouse models with large tumor burdens, most notably large, poorly immunogenic orthotopic hepatocellular carcinoma (HCC). DC show increased homing to lymphoid tissues and contribute to augmented memory T cells. Importantly, N1ND-painted serum exosomes from cancer patients also promote DC activation. Our study demonstrates the potency of TEX-N1ND to strengthen DC immunogenicity and to suppress large established tumors, and thus provides an avenue to improve DC-based immunotherapy.

摘要

针对基于树突状细胞（DC）的免疫疗法治疗大型已建立的肿瘤具有挑战性。用携带多种肿瘤相关抗原的肿瘤细胞衍生外泌体（TEX）激活 DC 可以增强肿瘤识别。添加一种有效的佐剂，高迁移率族核小体结合蛋白 1（HMGN1），可以提高 DC 激活 T 细胞的能力并提高疫苗效率。在这里，我们证明了通过外泌体锚定肽用 HMGN1 的功能域（TEX-N1ND）绘制的 TEX 增强了 DC 的免疫原性。TEX-N1ND 脉冲 DC（DC）在具有大肿瘤负担的不同同种型小鼠模型中引发持久的抗肿瘤免疫和肿瘤抑制，特别是大的、免疫原性差的原位肝癌（HCC）。DC 显示出向淋巴组织的归巢增加，并有助于增强记忆 T 细胞。重要的是，来自癌症患者的 N1ND 绘制的血清外泌体也促进了 DC 的激活。我们的研究证明了 TEX-N1ND 增强 DC 免疫原性和抑制大型已建立的肿瘤的功效，从而为改善基于 DC 的免疫疗法提供了一种途径。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1fb2/7156382/20e3b6d35ccb/41467_2020_15569_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1fb2/7156382/7f17ea04cc67/41467_2020_15569_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1fb2/7156382/8b617f083841/41467_2020_15569_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1fb2/7156382/b70a8fe4344c/41467_2020_15569_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1fb2/7156382/3d53c352089f/41467_2020_15569_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1fb2/7156382/3aa5c2f13bb9/41467_2020_15569_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1fb2/7156382/52c3da867acb/41467_2020_15569_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1fb2/7156382/20e3b6d35ccb/41467_2020_15569_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1fb2/7156382/7f17ea04cc67/41467_2020_15569_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1fb2/7156382/8b617f083841/41467_2020_15569_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1fb2/7156382/b70a8fe4344c/41467_2020_15569_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1fb2/7156382/3d53c352089f/41467_2020_15569_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1fb2/7156382/3aa5c2f13bb9/41467_2020_15569_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1fb2/7156382/52c3da867acb/41467_2020_15569_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1fb2/7156382/20e3b6d35ccb/41467_2020_15569_Fig7_HTML.jpg

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