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首页> 外文期刊>Immunology: An Official Journal of the British Society for Immunology >Melanoma cell lysate induces CCR7 expression and in vivo migration to draining lymph nodes of therapeutic human dendritic cells
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Melanoma cell lysate induces CCR7 expression and in vivo migration to draining lymph nodes of therapeutic human dendritic cells

机译：黑色素瘤细胞裂解物诱导CCR7表达并在体内迁移至治疗性人树突状细胞的引流淋巴结

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Summary: We have previously reported a novel method for the production of tumour-antigen-presenting cells (referred to as TAPCells) that are currently being used in cancer therapy, using an allogeneic melanoma-derived cell lysate (referred to as TRIMEL) as an antigen provider and activation factor. It was recently demonstrated that TAPCell-based immunotherapy induces T-cell-mediated immune responses resulting in improved long-term survival of stage IV melanoma patients. Clinically, dendritic cell (DC) migration from injected sites to lymph nodes is an important requirement for an effective anti-tumour immunization. This mobilization of DCs is mainly driven by the C-C chemokine receptor type 7 (CCR7), which is up-regulated on mature DCs. Using flow cytometry and immunohistochemistry, we investigated if TRIMEL was capable of inducing the expression of the CCR7 on TAPCells and enhancing their migration in vitro, as well as their in vivo relocation to lymph nodes in an ectopic xenograft animal model. Our results confirmed that TRIMEL induces a phenotypic maturation and increases the expression of surface CCR7 on melanoma patient-derived DCs, and also on the monocytic/macrophage cell line THP-1. Moreover, in vitro assays showed that TRIMEL-stimulated DCs and THP-1 cells were capable of migrating specifically in the presence of the CCR7 ligand CCL19. Finally, we demonstrated that TAPCells could migrate in vivo from the injection site into the draining lymph nodes. This work contributes to an increased understanding of the biology of DCs produced ex vivo allowing the design of new strategies for effective DC-based vaccines for treating aggressive melanomas.
机译：摘要：我们以前已经报道了一种新方法，该方法可用于生产目前正在癌症治疗中使用的肿瘤抗原呈递细胞（称为TAPCells），该方法使用了同种异体黑素瘤衍生的细胞裂解液（称为TRIMEL）作为抗原提供者和激活因子。最近证明基于TAPCell的免疫疗法可诱导T细胞介导的免疫反应，从而改善IV期黑色素瘤患者的长期存活率。在临床上，树突状细胞（DC）从注射部位迁移到淋巴结是有效抗肿瘤免疫的重要要求。 DC的这种动员主要是由7型C-C趋化因子受体（CCR7）驱动的，成熟型DC上调了它的表达。使用流式细胞仪和免疫组织化学，我们调查了TRIMEL是否能够诱导TAPCells上CCR7的表达并增强其在体外的迁移，以及它们在异位异种移植动物模型中的体内淋巴结重定位。我们的结果证实，TRIMEL诱导表型成熟，并在源自黑素瘤患者的DC以及单核/巨噬细胞THP-1上增加表面CCR7的表达。此外，体外测定表明，在CCR7配体CCL19存在下，TRIMEL刺激的DC和THP-1细胞能够特异性迁移。最后，我们证明了TAPCells可以在体内从注射部位迁移到引流淋巴结中。这项工作有助于加深对离体产生的DC生物学的了解，从而可以设计出有效的基于DC的疫苗来治疗侵袭性黑素瘤的新策略。

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