灭活同种异基因白细胞输注抗肿瘤转移的研究

Anti-tumor metastatic effects of inactivated allogeneic leukocytes infusion

目的:探讨灭活MHC不相合同种异基因白细胞输注(ALI)的抗肿瘤转移效应及其相关机制。方法:MMC灭活的同种异基因白细胞输注治疗B16-F10及LLC荷瘤小鼠,细胞毒实验鉴定ALI抗肿瘤中效应细胞;小鼠血清细胞因子检测分析ALI治疗后在宿主体内产生的免疫效应。结果:新鲜制备或灭活ALI治疗B16-F10人工肺转移小鼠肺质量分别为0.26和0.35 g,PBS组为0.64 g(两治疗组分别与PBS组相比,P<0.001);小鼠平均生存期分别较PBS组延长20.625和12.75 d。灭活ALI治疗LLC自发肺转移小鼠肺质量为0.18 g,PBS组为0.43 g,P=0.007;ALI治疗组62.5%小鼠长期生存(>120 d);小鼠脾单个核细胞对LLC和YAC-1杀伤活性分别为20%和46.4%(效靶比为60∶1);ALI治疗后小鼠血清中IL-2和IFN-γ浓度分别是PBS组小鼠的3.2和10.6倍(分别与PBS组相比,P<0.001),IL-4和IL-10浓度与PBS组相比差异无统计学意义。结论:灭活同种异基因白细胞输注可诱导抗肿瘤免疫反应,该方法有望成为一种新的抗肿瘤转移疗法。

OBJECTIVE： To investigate the anti-metastatic activity and mechanisms of infusions of inactivated MHC-mismatched allogeneic leukocytes.METHODS： B16-F10 or LLC tumor bearing C57BL/6 mice were treated with mitomycin C inactivated allogeneic leukocytes infusion（ALI）.The effector cells involved in the ALI antitumor activity were identified through cell-mediated cytotoxicity assay.The immunological mechanisms of antitumor effect were analyzed by cytokines detection of murine serum.RESULTS： The lung weights of fresh generated or inactivated ALI treated B16-F10 artificial metastatic mice were 0.26 g and 0.35 g respectively,which in the PBS group was 0.64 g（both treatment groups compared with PBS group,P0.001）.Mean survival time prolonged 20.625 and 12.75 days,being more than that of the PBS group respectively.The lung weight of inactivated ALI treated LLC spontaneous metastatic mice was 0.18 g,which of the PBS group was 0.43 g（P=0.007）;62.5% mice obtained long-term survival（120 days） in the ALI group;the cytotoxicities of mononuclear cells of murine splenocytes against LLC and YAC-1 tumor cells were 20% and 46.4% respectively（effector versus target ratio=60∶1）;the serum levels of IL-2 and IFN-γ following ALI treatment were 3.2 and 10.6 folds versus PBS group（compared with PBS group,P0.001）.For the concentrations of IL-4 and IL-10,however,there were no statistic differences compared with the PBS group.CONCLUSIONS： Mitotically inactivated allogeneic leukocytes administered may induce antitumor immunological responses.The transfusion of mitotically allogeneic leukocytes should be developed further as a novel therapeutic anti-metastatic approach.