化学治疗作为肿瘤常规治疗的中坚力量,其目的是杀伤肿瘤细胞,但由于化疗药物对机体免疫系统也有一定程度的杀伤或抑制效应,因而以往普遍认为化疗与免疫治疗在功能上是拮抗的。新近研究发现,一些化疗药物可以通过增强肿瘤细胞免疫原性、...化学治疗作为肿瘤常规治疗的中坚力量,其目的是杀伤肿瘤细胞,但由于化疗药物对机体免疫系统也有一定程度的杀伤或抑制效应,因而以往普遍认为化疗与免疫治疗在功能上是拮抗的。新近研究发现,一些化疗药物可以通过增强肿瘤细胞免疫原性、促进肿瘤细胞释放内源性危险信号、以及抑制调节性T细胞(regulatory T cell,Treg)等机制增强肿瘤的免疫原性,介导抗肿瘤免疫,对肿瘤的整体化疗效果有其独特的贡献。依据化疗后肿瘤细胞免疫原性的不同变化,设计相应的治疗方案,将化疗和免疫治疗有机结合,将最终提高肿瘤的治疗效果。展开更多
Objective： To investigate the antitumor activity of tumor lysate-pulsed dendritic cells vaccine in RM-1 prostate cancer mice model with the survival time of mice calculated and the tumor size measured in DC vaccine t...Objective： To investigate the antitumor activity of tumor lysate-pulsed dendritic cells vaccine in RM-1 prostate cancer mice model with the survival time of mice calculated and the tumor size measured in DC vaccine therapy. Methods： C57BL/6 mice were immunized on the dorsal flank by s.c. inoculation of Lysate-DC, ova-DC, and non-DC on day -7. On day 0, 2× 10^6cells of RM-1 tumor cells （H-2b） were injected s.c. in C57BL/6 mice pre-treated by s.c. inoculation of modified DCs, correspondingly. DTH assay was performed with modified DCs. In partial test, for the determination of which immune cells were required for antitumor activity, mice were immunodepleted of CD4, CDS, or natural killer （NK） NK1.1 cells with the corresponding monoclonal antibodies. The survival time of nude mice loaded with tumor cells was calculated and the size of tumor measured. Results： In RM-1 mice prostate cancer model, immunized with lysate-DC, compared with ova-DC and non-DC, the pre-infection vaccine resulted in 100% clearance of primary tumors, whereas on day 0 of injection vaccine cleared 40-60% of primary tumors. On day 0, C57BL/6 mice （H-2b） were immunized with Lysate-DC, compared with ova-DC and non-DC by caudal vein injection, then on day 15, RM-1 cells were inoculated. On day 30, average diameters of tumor in different groups of modified DC were 23.7±5.4 mm, 22.1±4.9 mm, 4.3±2.6 mm, respectively. Lysate-DC, compared with ova-DC and non-DC, can greatly depressed RM-1 tumor cell growth （P〈0.01）. The mean survival time of C57BL/6 mice in Lysate-DC, ova-DC and non-DC groups were 15.8±2.6, 16.6±3.2, 39.0±5.6, respectively, and there was a significant difference in the mean survival time in lysate-DC group between ova-DC and non-DC group （P〈0.01）. DTH test showed that lysate-DC could prime T lymphocyte and elicit tumor antigen specific immune response, and over 80% mice in groups of lysate-DC showed obvious swelling in their foot pad. This response was strengthened with repeating inoculation, whereas DTH response was not seen in control group. In vivo depletion of NK cells resulted in a 40-60% reduction in growth suppression within the primary tumor, and depletion of CD4^＋ cells resulted in a 20% reduction in growth suppression. Conclusion： The minor lysate-pulsed dendritic cells vaccine could elicit antitumor activity in RM-1 loaded C57BL/6 mice, and prolong the duration of RM-1 loaded C57BL/6 mice. So DC-based immunotherapy with hormone-refractory prostate carcinoma yielded protective immunity, generated efficient cellular antitumor responses, thereby providing further preclinical support for feasible immunotherapy approaches for prostate cancer.展开更多
文摘化学治疗作为肿瘤常规治疗的中坚力量,其目的是杀伤肿瘤细胞,但由于化疗药物对机体免疫系统也有一定程度的杀伤或抑制效应,因而以往普遍认为化疗与免疫治疗在功能上是拮抗的。新近研究发现,一些化疗药物可以通过增强肿瘤细胞免疫原性、促进肿瘤细胞释放内源性危险信号、以及抑制调节性T细胞(regulatory T cell,Treg)等机制增强肿瘤的免疫原性,介导抗肿瘤免疫,对肿瘤的整体化疗效果有其独特的贡献。依据化疗后肿瘤细胞免疫原性的不同变化,设计相应的治疗方案,将化疗和免疫治疗有机结合,将最终提高肿瘤的治疗效果。
基金Supported by medical funds of Shanghai Science and Technology Commission
文摘Objective： To investigate the antitumor activity of tumor lysate-pulsed dendritic cells vaccine in RM-1 prostate cancer mice model with the survival time of mice calculated and the tumor size measured in DC vaccine therapy. Methods： C57BL/6 mice were immunized on the dorsal flank by s.c. inoculation of Lysate-DC, ova-DC, and non-DC on day -7. On day 0, 2× 10^6cells of RM-1 tumor cells （H-2b） were injected s.c. in C57BL/6 mice pre-treated by s.c. inoculation of modified DCs, correspondingly. DTH assay was performed with modified DCs. In partial test, for the determination of which immune cells were required for antitumor activity, mice were immunodepleted of CD4, CDS, or natural killer （NK） NK1.1 cells with the corresponding monoclonal antibodies. The survival time of nude mice loaded with tumor cells was calculated and the size of tumor measured. Results： In RM-1 mice prostate cancer model, immunized with lysate-DC, compared with ova-DC and non-DC, the pre-infection vaccine resulted in 100% clearance of primary tumors, whereas on day 0 of injection vaccine cleared 40-60% of primary tumors. On day 0, C57BL/6 mice （H-2b） were immunized with Lysate-DC, compared with ova-DC and non-DC by caudal vein injection, then on day 15, RM-1 cells were inoculated. On day 30, average diameters of tumor in different groups of modified DC were 23.7±5.4 mm, 22.1±4.9 mm, 4.3±2.6 mm, respectively. Lysate-DC, compared with ova-DC and non-DC, can greatly depressed RM-1 tumor cell growth （P〈0.01）. The mean survival time of C57BL/6 mice in Lysate-DC, ova-DC and non-DC groups were 15.8±2.6, 16.6±3.2, 39.0±5.6, respectively, and there was a significant difference in the mean survival time in lysate-DC group between ova-DC and non-DC group （P〈0.01）. DTH test showed that lysate-DC could prime T lymphocyte and elicit tumor antigen specific immune response, and over 80% mice in groups of lysate-DC showed obvious swelling in their foot pad. This response was strengthened with repeating inoculation, whereas DTH response was not seen in control group. In vivo depletion of NK cells resulted in a 40-60% reduction in growth suppression within the primary tumor, and depletion of CD4^＋ cells resulted in a 20% reduction in growth suppression. Conclusion： The minor lysate-pulsed dendritic cells vaccine could elicit antitumor activity in RM-1 loaded C57BL/6 mice, and prolong the duration of RM-1 loaded C57BL/6 mice. So DC-based immunotherapy with hormone-refractory prostate carcinoma yielded protective immunity, generated efficient cellular antitumor responses, thereby providing further preclinical support for feasible immunotherapy approaches for prostate cancer.
