吞噬凋亡肿瘤细胞的树突细胞疫苗抗肿瘤效果观察

目的：研究吞噬凋亡肿瘤细胞的树突细胞疫苗的抗肿瘤效果，以确定一种有效的树突细胞疫苗。方法：由黑色素瘤细胞（BLb-10)生成凋亡细胞，树突细胞（DC）与凋亡肿瘤细胞培育后，收集和提纯吞噬凋亡肿瘤细胞的树突细胞，再对其表型变化及抗肿瘤效果进行检测，并与加肿瘤细胞肽（mTRP2)的树突细胞的结果比较。结果：吞噬凋亡肿瘤细胞后，DC更加成熟。表现出促炎症细胞因子（IL－1，IL－6，TNF－α，IFN--γ和GM－CSF），趋化因子（MIP－1，MIP－1和MIP－2），细胞表面分子（HMC-Ⅱ，CD11bCD40和CD86）以及某些趋化因子受体（CCR7）表达增加而某些趋化因子受体（CCR2和CCR5）表达减少。吞噬了凋亡黑色素瘤细胞的树突细胞疫能（i）更强地刺激体外T细胞增生，（ii）诱导体内Th1型免疫反应而导致更有效的肿瘤特异细胞毒CD8＋细胞 介导的免疫，和（iii)防止了免疫鼠肺肿瘤转移，而加肿瘤细胞肽的树突细胞疫苗只能减少免疫鼠的肺肿瘤转移。结论：吞噬凋亡黑色素瘤细胞的树突细胞疫苗为癌细胞疫苗研究提供了新的途径。

EFFICIENT ANTITUMOR IMMUNITY DERIVED FROM MATURATION OF DENDRITIC CELLS THAT HAD PHAGOCYTOSED APOPTOTIC TUMOR CELLS

Objective: In order to define an efficient DC vaccine strategy, the efficiency of antitumor immunity derived fromdendritic cells (DCs) that had phagocytosed apoptotic tumor cells was investigated. Methods: after incubation with apoptotic tumorcells prepared from BL 6 - 10 melanoma cells, DCs that had phagocytosed apoptotic tumor cells were harvested and purified. Then their phenotypic expressions and antitumor efficiency were investigated and compared with those of DCs pulsed with mTRP2 pep-tide. Results: Our data showed that phagocytosis of apoptotic tumor cells resulted in maturation of DCs with up - regulated expression of proinflammatory cytokines (IL - 1, IL- 6, TNT- α, IFN - γ and GM - CSF), chemokites (MIP- 1α,MIP - 1β and MIP- 2) ,the CC chemokine receptor CCR7 and the cell surface molecules (MHC class Ⅱ, CD11β, CD40 and CD86), and down-regulated expression of the CC chemokine receptors CCR2 and CCR5. Our data also showed that vaccination with DCs that hadphagocytosed apoptotc BL6- 10 cells was able to (I) more strongly stimulate allogeneic T- cell proliferation in vitro, (ii) induceand in vivo Thl - type immune response leading to more efficient tumor- specific cytotoxic CD8 + T- cell - mediated immunityand (iii) eradicate lung metastases in all 6 vaccinated mice compared with mice vaccinated with DCs pulsed with the tumormTRP2 peptide, in which lung metastases were reduced (mean number of 16 per mouse) but not completely eradicated.Conclu sion: DCs that had phagocytosed apoptotic tumor cells appear to offer new trategies in DC cancer vaccines.