Apoptotic, necrotic, or fused tumor cells:: An equivalent source of antigen for dendritic cell loading
Apoptotic, necrotic, or fused tumor cells:: An equivalent source of antigen for dendritic cell loading
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DOI：
10.1007/s10495-006-8765-0
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发表时间：
2006-09-01
期刊：
影响因子：
7.2
通讯作者：
Bonnotte, Bernard
中科院分区：
文献类型：
--
作者：
Larmonier, Nicolas;Merino, Delphine;Bonnotte, Bernard
确定树突状细胞（DC）的肿瘤抗原负载的最有效策略仍然是癌症免疫治疗方案中的一个挑战。已经证明，自体死亡的肿瘤细胞构成了可接受的多种肿瘤相关抗原（TAA）的来源，以脉冲DC。然而，诱导细胞死亡的最佳方法，将导致有效的内吞作用和激活的DC仍然存在争议。在这项研究中，我们诱导并定义了3种不同的肿瘤细胞死亡机制（凋亡，坏死和融合介导的细胞死亡），并研究了它们对DC的差异作用。骨髓来源的DC表现出对原发性凋亡、坏死或融合死亡肿瘤细胞的相当的摄取。此外，癌细胞死亡的不同模式在激活转录因子NF-κ B和STAT 1以及成熟DC方面具有类似的潜力，导致免疫T细胞的同样有效的刺激。因此，目前的研究提供了关于使用死亡的完整肿瘤细胞作为有效的主动抗癌免疫治疗的抗原来源的进一步信息。
The identification of the most efficient strategy for tumor antigen loading of dendritic cells (DCs) remains a challenge in cancer immunotherapy protocols. Autologous dead tumor cells have been demonstrated to constitute an acceptable source of multiple tumor-associated antigens (TAA) to pulse DCs. However the optimal approach for inducing cell death that would lead to effective endocytosis and activation of DCs remains controversial. In this study we have induced and defined 3 distinct mechanisms of tumor cell death (apoptosis, necrosis and fusion-mediated cell death), and investigated their differential effects on DCs. Bone marrow-derived DCs demonstrated comparable uptake of primary apoptotic, necrotic, or fused dead tumor cells. Furthermore, the distinct modes of cancer cell death had analogous potential in activating the transcription factors NF-kappa B and STAT1 and in maturing DCs, resulting in an equally effective stimulation of immune T cells. The current study therefore provides further informations on the use of dead whole tumor cells as antigen sources for effective active anti-cancer immunotherapy.