Yang S, Darrow T L, Vervaert C E, Seigler H F
Duke University Medical Center, Department of Surgery, Durham, North Carolina 27710, USA.
Cell Immunol. 1997 Jul 10;179(1):84-95. doi: 10.1006/cimm.1997.1151.
Dendritic cells (DC) are highly efficient antigen-presenting cells able to capture, process, and present antigens to naive and primed T-cells. In this study, we have investigated the ability of DC, derived from murine bone marrow and pulsed with tumor cell extracts, to induce regression of preexisting tumors. In an experimental model of B16 melanoma in B6 mice, a significant reduction in metastatic nodules in the lungs was observed in tumor-bearing animals treated with either DC alone or DC pulsed with tumor extracts. Kinetic studies demonstrate that the efficacy of these tumor vaccines is inversely related to tumor burden. In this model, tumor-specific cytotoxic T-cells (CTL) could also be induced in vitro from spleen cells derived from tumor-bearing animals treated with DC pulsed with tumor extracts. Untreated mice had no CTL. Furthermore, DC alone elicited tumor-specific CTL responses in tumor-bearing mice, but not in naive mice. Immune cell depletion experiments show that the therapeutic effects of DC are primarily mediated by CD8+ T-cells, while CD4+ T-cells and NK cells are involved in DC-mediated antitumor immunity to a limited extent. These results illustrate the potential use of DC and DC pulsed with tumor extracts as potent therapeutic reagents for cancer and provide a rationale for using DC in vivo to eliminate disseminated tumors or residual tumor deposits following surgery.
树突状细胞（DC）是高效的抗原呈递细胞，能够捕获、处理抗原并将其呈递给未致敏和已致敏的T细胞。在本研究中，我们调查了源自小鼠骨髓并用肿瘤细胞提取物脉冲处理的DC诱导已存在肿瘤消退的能力。在B6小鼠的B16黑色素瘤实验模型中，在用单独的DC或用肿瘤提取物脉冲处理的DC治疗的荷瘤动物中，观察到肺部转移结节显著减少。动力学研究表明，这些肿瘤疫苗的疗效与肿瘤负荷呈负相关。在该模型中，也可以从用肿瘤提取物脉冲处理的DC治疗的荷瘤动物的脾细胞中体外诱导肿瘤特异性细胞毒性T细胞（CTL）。未治疗的小鼠没有CTL。此外，单独的DC在荷瘤小鼠中引发肿瘤特异性CTL反应，但在未致敏小鼠中则不然。免疫细胞清除实验表明，DC的治疗作用主要由CD8 + T细胞介导，而CD4 + T细胞和NK细胞在DC介导的抗肿瘤免疫中仅起有限作用。这些结果说明了DC和用肿瘤提取物脉冲处理的DC作为癌症有效治疗试剂的潜在用途，并为在体内使用DC消除播散性肿瘤或手术后残留的肿瘤沉积物提供了理论依据。
