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首页> 外文期刊>Journal of immunotherapy >Splenic Dendritic Cells Involved in Cross-Tolerance of Tumor Antigens Can Play a Stimulatory Role in Adoptive T-Cell Therapy
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Splenic Dendritic Cells Involved in Cross-Tolerance of Tumor Antigens Can Play a Stimulatory Role in Adoptive T-Cell Therapy

机译：涉及肿瘤抗原交叉耐受的脾树突状细胞可在过继性T细胞治疗中发挥刺激作用

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摘要

Circulating antigens released from tumor cells can drain into the spleen and be acquired by resident antigen-presenting cells (APCs). Here, we examined the ability of splenic dendritic cells to cross-present tumor antigens to CD8(+) T cells and investigated the effects that this has on T-cell therapy in a murine model of lymphoma. In the presence of established lymphoma, langerin (CD207)-expressing CD8(+) dendritic cells acquired, processed, and cross-presented tumor antigens to naive CD8(+) T cells. Although this resulted in initial T-cell proliferation, the T-cell population failed to expand measurably over the following days, and tumor-free survival was actually improved when langerin-expressing cells were depleted. In contrast, following adoptive T-cell therapy with in vitro-activated CD8(+) T cells, marked antitumor activity was observed and associated with accumulation of activated antigen-specific CD8(+) T cells in the spleen and blood, whereas tumor protection and T-cell accumulation were significantly reduced in animals depleted of langerin-expressing cells. Therefore, although resident APCs that acquire tumor antigens may induce tolerance in naive cells in the absence of further stimuli, they can play an important role in promoting antitumor immunity during the course of T-cell therapy. It is possible that further therapeutic benefit will result from improving the activation status of these APCs.
机译：从肿瘤细胞释放的循环抗原可以排入脾脏，并被常驻抗原呈递细胞（APC）获得。在这里，我们检查了脾脏树突状细胞将肿瘤抗原交叉呈递给CD8（+）T细胞的能力，并研究了其对小鼠淋巴瘤模型T细胞治疗的影响。在已建立的淋巴瘤的存在下，表达橘皮蛋白（CD207）的CD8（+）树突状细胞获得，加工并交叉呈递给天然CD8（+）T细胞。尽管这导致了最初的T细胞增殖，但是T细胞在接下来的几天中无法进行可扩展的扩增，而当表达Langerin的细胞被耗尽后，无肿瘤的存活实际上得到了改善。相反，在采用体外活化的CD8（+）T细胞进行过继T细胞治疗后，观察到明显的抗肿瘤活性，并且与脾脏和血液中活化的抗原特异性CD8（+）T细胞积累有关，而肿瘤保护在缺乏表达橘皮素的细胞中，T细胞和T细胞的积累显着减少。因此，尽管获得肿瘤抗原的常驻APC可以在没有进一步刺激的情况下诱导幼稚细胞的耐受性，但它们在T细胞治疗过程中可促进抗肿瘤免疫性发挥重要作用。改善这些APC的激活状态可能会带来进一步的治疗益处。

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