DeMatos P, Abdel-Wahab Z, Vervaert C, Seigler H F
Department of Surgery, Duke University Medical Center, Durham, North Carolina 27710, USA.
Cell Immunol. 1998 Apr 10;185(1):65-74. doi: 10.1006/cimm.1998.1277.
Dendritic cells (DC) are specialized antigen-presenting cells that can activate naive and mature T-cells, induce cellular immunity, and stimulate strong antitumor reactions in vivo. This study was undertaken to examine the function of DC vaccines in suppressing the growth of hepatic metastases in C57BL/6 mice. Experimental mice received two i.v. doses of 1 x 10(6) bone marrow-derived DC, either unpulsed or pulsed with MCA-106 fibrosarcoma cell lysates, on days -14 and -7. Controls were injected with HBSS. Hepatic metastases were established on day 0 through intrasplenic injections of 1 x 10(5) MCA-106 tumor cells. Animals were sacrificed on day 21 and their livers were excised to assess tumor burden. Splenocytes from DC-treated groups were cytotoxic against MCA-106 cells, but not against the L929 and CT26 (syngeneic fibroblast and colon tumor, respectively) cell lines. All control mice developed grossly evident hepatic metastases, while 62 and 44% of the mice receiving MCA-106 cell lysate-pulsed DC and unpulsed DC vaccines, respectively, were completely free of tumor. Mean hepatic mass for the controls, including tumor, was almost double that for treated animals. Antibody depletion of either CD4+ or CD8+ lymphocytes abrogated the protective effect of the vaccine. This study demonstrates that immunization with DC confers cellular immunity, with both CD4+ and CD8+ T-cells playing a significant role, and impedes the subsequent establishment and growth of hepatic metastases in mice. The antitumor capabilities of DC justify their use in immunotherapeutic vaccines against human cancers.
树突状细胞（DC）是专门的抗原呈递细胞，能够激活幼稚和成熟的T细胞，诱导细胞免疫，并在体内刺激强烈的抗肿瘤反应。本研究旨在检测DC疫苗在抑制C57BL/6小鼠肝转移瘤生长中的作用。实验小鼠在第-14天和第-7天接受两次静脉注射，剂量为1×10⁶个骨髓来源的DC，分别为未脉冲或用MCA-106纤维肉瘤细胞裂解物脉冲处理的DC。对照组注射HBSS。在第0天通过脾内注射1×10⁵个MCA-106肿瘤细胞建立肝转移瘤。在第21天处死动物，切除肝脏以评估肿瘤负荷。DC处理组的脾细胞对MCA-106细胞具有细胞毒性，但对L929和CT26（分别为同基因成纤维细胞和结肠肿瘤细胞系）细胞系无细胞毒性。所有对照小鼠均出现明显的肝转移瘤，而分别接受MCA-106细胞裂解物脉冲处理的DC疫苗和未脉冲处理的DC疫苗的小鼠中，62%和44%完全没有肿瘤。包括肿瘤在内的对照组平均肝脏质量几乎是处理组动物的两倍。CD4⁺或CD8⁺淋巴细胞的抗体清除消除了疫苗的保护作用。本研究表明，用DC免疫可赋予细胞免疫，CD4⁺和CD8⁺T细胞均发挥重要作用，并阻碍小鼠肝转移瘤的后续形成和生长。DC的抗肿瘤能力证明了它们在针对人类癌症的免疫治疗疫苗中的应用价值。
