树突状细胞负载前列腺癌细胞抗原后的抗肿瘤免疫作用

Anti-tumor response of dendritic cells after pulsed with whole tumor cell lysates of prostate cancer cell line

目的 探讨小鼠树突状细胞 (DC)负载前列腺癌细胞株RM 1的裂解产物后 ,诱导特异性细胞毒T淋巴细胞(CTL)及其抗肿瘤的免疫作用。方法 将RM 1细胞的裂解产物 (T lysate)作为肿瘤抗原负载小鼠骨髓来源的DC ,构建DC瘤苗 (T lysate/DC) ,采用流式细胞术和四唑氮蓝 (MTT)还原法检测其免疫活性 ;ELISA法检测其诱导细胞因子白介素(IL) 2和γ 干扰素 (IFN γ)的作用 ;体内实验检测DC瘤苗的抗肿瘤免疫治疗作用和免疫保护作用。结果 DC负载RM 1细胞的裂解产物后 ,其主要组织相容性复合物 (MHC Ⅰ、Ⅱ )及共刺激分子 (B7 1、B7 2 )的表达明显增高 ;T lysate/DC能够诱导小鼠产生RM 1特异性CTL ,使细胞上清液中IL 2和IFN γ水平升高 ,对小鼠具有免疫保护作用 ,并能有效抵抗肿瘤细胞的攻击 ;经T lysate/DC治疗的荷瘤小鼠瘤体生长减慢 ,存活期延长 ,瘤体出现坏死和炎细胞浸润。 结论 DC负载前列腺癌细胞裂解产物后 ,能够有效诱导抗肿瘤免疫反应 ,为前列腺癌的临床治疗提供了新策略。

Objective To appraise the immune response against prostate cancer based on dendritic cells (DC) pulsed with whole tumor lysate (T lysate). Methods Mouse bone marrow DCs were pulsed with prostate cancer cell line RM 1's whole lysate at a ratio of three tumor cells to one DC. The surface phenotypes of DC vaccine (T lysate/DC) were detected by FACS and the cytotoxicity of CTL was assayed by MTT method. The T lysate/DC was used to vaccinate syngeneic mice or to treat the preestablished tumor bearing mice with prostate cancer. Results The DC pulsed with T lysate increased the expressions of MHC Ⅰ, MHC Ⅱ, CD80(B7 1), CD86(B7 2). Immunization of mice with the DC vaccine could enhance the cytotoxicity of CTL, increase the production of IL 2 and interferon γ. The mice immunized with DC vaccine also exhibited resistance to tumor challenge more effectively. In the preestablished tumor bearing mice, immunization with T lysate/DC inhibited the tumor growth significantly showing the tumor mass contained of necrosis and inflammatory cell infiltration. Conclusion DC pulsed with whole tumor lysate is more potent in the induction of protective and therapeutic anti tumor immunity.