INSERM Unité Mixte de Recherche 866, Institut de Recherche Fédératif 100, Faculté de Médecine, 21079 Dijon, France.
J Immunol. 2011 Sep 1;187(5):2775-82. doi: 10.4049/jimmunol.1004146. Epub 2011 Jul 29.
Known for years as professional APCs, dendritic cells (DCs) are also endowed with tumoricidal activity. This dual role of DC as killers and messengers may have important implications for tumor immunotherapy. However, the tumoricidal activity of DCs has mainly been investigated in animal models. Cancer cells inhibit antitumor immune responses using numerous mechanisms, including the induction of immunosuppressive/ tolerogenic DCs that have lost their ability to present Ags in an immunogenic manner. In this study, we evaluated the possibility of generating tumor killer DCs from patients with advanced-stage cancers. We demonstrate that human monocyte-derived DCs are endowed with significant cytotoxic activity against tumor cells following activation with LPS. The mechanism of DC-mediated tumor cell killing primarily involves peroxynitrites. This observed cytotoxic activity is restricted to immature DCs. Additionally, after killing, these cytotoxic DCs are able to activate tumor Ag-specific T cells. These observations may open important new perspectives for the use of autologous cytotoxic DCs in cancer immunotherapy strategies.
多年来被认为是专业 APCs 的树突状细胞 (DCs) 也具有杀肿瘤活性。DC 作为杀手和信使的这种双重作用可能对肿瘤免疫治疗具有重要意义。然而，DC 的杀肿瘤活性主要在动物模型中进行了研究。癌细胞使用多种机制抑制抗肿瘤免疫反应，包括诱导丧失以免疫原性方式呈递 Ag 能力的免疫抑制/耐受 DC。在这项研究中，我们评估了从晚期癌症患者中产生肿瘤杀伤 DC 的可能性。我们证明，人单核细胞衍生的 DC 在 LPS 激活后对肿瘤细胞具有显著的细胞毒性活性。DC 介导的肿瘤细胞杀伤的机制主要涉及过氧亚硝酸盐。这种观察到的细胞毒性活性仅限于未成熟的 DC。此外，在杀伤后，这些细胞毒性 DC 能够激活肿瘤 Ag 特异性 T 细胞。这些观察结果可能为在癌症免疫治疗策略中使用自体细胞毒性 DC 开辟重要的新视角。
