Tumor cell-derived autophagosomes (DRibbles)-activated B cells induce specific naïve CD8+ T cell response and exhibit antitumor effect
Tumor cell-derived autophagosomes (DRibbles)-activated B cells induce specific naïve CD8+ T cell response and exhibit antitumor effect
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DOI：
10.1007/s00262-020-02695-5
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发表时间：
2020-08
期刊：
影响因子：
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通讯作者：
Tianyu Zhang;Hongyan Ren;Ning Pan;Huixia Dong;Simin Zhao;Zhifa Wen;Xuru Wang;Lixin Wang
中科院分区：
文献类型：
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作者：
Tianyu Zhang;Hongyan Ren;Ning Pan;Huixia Dong;Simin Zhao;Zhifa Wen;Xuru Wang;Lixin Wang
树突状细胞（DC）疫苗是一种有效的肿瘤免疫治疗方法，其临床前和临床研究均已证实。然而，DC分离和培养的局限性阻碍了其实践，并促进了其他抗原呈递细胞（APC）来源的发展，以履行这一作用。我们以前的研究表明，负载肿瘤细胞来源的自噬体的B细胞，我们将其命名为DRibbles（deficient ribosomal products-containing blebs），可以重新激活DC诱导的效应T细胞应答。在这项研究中，研究了Dribble负载的B细胞在引发幼稚CD 8 +T细胞应答和控制肿瘤中的作用。我们发现DRibble上的高迁移率族蛋白B1（HMGB 1）参与DRibble诱导的B细胞活化，DRibble通过小窝介导的内吞途径触发B细胞的吞噬作用。通过使用OT-I小鼠来源的T细胞，我们证明了DRibble负载的B细胞可以在体外和离体激活特异性幼稚CD 8 +T细胞。在荷瘤小鼠模型中，DRibble负载的B细胞引起全身抗肿瘤免疫并显著抑制肿瘤生长。此外，DRibble负载的B细胞与CpG和抗CD 40刺激相结合时，其抗肿瘤功效增强。这些结果表明，DRibble负载的B细胞代表了一种可行的和实用的治疗性疫苗接种策略，可能对肿瘤免疫治疗具有重要的临床意义。
Dendritic cell (DC) vaccine has been proved to be an effective way in cancer immunotherapy in both preclinical and clinical studies. However, limitations in DC isolation and culture have hampered its practice and promoted the development of other antigen-presenting cells (APCs) sources to fulfill that role. Our previous studies have shown that B cells loaded by tumor cell-derived autophagosomes, which we named as DRibbles (defective ribosomal products-containing blebs), could reactivate DC-induced effector T cell response. In this study, the roles of DRibble-loaded B cells in priming naïve CD8+T cell responses and controlling tumors were investigated. We found that high-mobility group box 1 protein (HMGB1) on DRibbles was involved in DRibble-induced B cell activation, and the DRibble-triggered B cell phagocytosis via the caveolae-mediated endocytosis pathway. By using OT-I mouse-derived T cells, we demonstrated that DRibble-loaded B cells could activate specific naïve CD8+T cells in vitro and ex vivo. In a tumor-bearing mouse model, DRibble-loaded B cells elicited systemic antitumor immunity and significantly suppressed the tumor growth. Moreover, the antitumor efficacy of DRibble-loaded B cells was enhanced when they were combined with CpG and anti-CD40 stimulation. These results suggest that DRibble-loaded B cells represent a viable and practical therapeutic vaccination strategy that might have important clinical implications for tumor immunotherapy.