Alarmin-painted exosomes elicit persistent antitumor immunity in large established tumors in mice
Alarmin-painted exosomes elicit persistent antitumor immunity in large established tumors in mice
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警报素染色的外泌体在小鼠体内的大型肿瘤中引发持久的抗肿瘤免疫
DOI：
10.1038/s41467-020-15569-2
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发表时间：
2020-04-14
影响因子：
16.6
通讯作者：
Yin, HaiFang
中科院分区：
文献类型：
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作者：
Zuo, Bingfeng;Qi, Han;Yin, HaiFang
治疗大的已建立的肿瘤对于基于树突状细胞（DC）的免疫疗法是具有挑战性的。用携带多种肿瘤相关抗原的肿瘤细胞来源的外泌体（TEX）活化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（HMGN 1），增强了DC激活T细胞的能力，提高了疫苗的效率。在这里，我们证明了通过外泌体锚肽涂有HMGN 1（TEX-N1 ND）的功能结构域的TEX增强DC免疫原性。TEX-N1 ND脉冲的DC（DCTEX-N1 ND）在具有大肿瘤负荷的不同同基因小鼠模型（最显著的是大的、免疫原性差的原位肝细胞癌（HCC））中引发持久的抗肿瘤免疫和肿瘤抑制。DCTEX-N1 ND显示增加的淋巴组织归巢，并有助于增强记忆T细胞。重要的是，来自癌症患者的N1 ND涂染的血清外泌体也促进DC活化。我们的研究证明了TEX-N1 ND增强DC免疫原性和抑制大型肿瘤的潜力，从而为改善基于DC的免疫治疗提供了一条途径。
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 (DCTEX-N1ND) 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). DCTEX-N1NDshow 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.