乳腺癌干细胞的树突状细胞疫苗对细胞毒性T淋巴细胞增殖的影响

Dendritic cell vaccine prepared with breast cancer stem-like cells activates cytotoxic T lymphocytes

目的探讨加载人类乳腺癌干细胞(BSC)的树突状细胞(DC)疫苗对细胞毒性T淋巴细胞(CTL)活化效果的影响。方法从11例乳腺癌患者中分离并评价BSC,探讨BSC作为DC疫苗抗原的适用性,并在体外评估了杀伤BSC的能力。结果BSC表达高水平的干细胞相关分子CD44^+、CD24-和CD133^+,乳腺癌贴壁细胞表达CD44^+、CD24^+和低CD133^+。在体内,富集的乳腺癌细胞球表现出比贴壁细胞更强的致瘤能力。使用BSC裂解物的DC疫苗接种引发针对BSC的特异性T细胞应答。DC疫苗接种刺激Th1应答并诱导IFN-γ产生,与活化的CTL数量呈正相关。结论乳腺癌细胞球细胞具有干细胞特性和强致瘤功能,使用BSC抗原的DC接种可引发有效的抗原特异性Th1应答,进一步激活抗原特异性CTL并诱导IFN-γ产生。

Objective To investigate the effect of dendritic cell（DC） vaccine prepared with human breast cancer stem cells（BSCs） on the activation of cytotoxic T lymphocytes（CTLs）. Methods The BSCs were isolated from breast cancer patients,and the human DCs were stimulated with BSC lysates to prepare the DC vaccine against human BSC. The activity of cytotoxic T cells against BSC in vitro was tested. Results The BSCs expressed high levels of stem cell-associated molecules CD44~＋/CD24-and CD133~＋, while adherent cells expressed CD44~＋/CD24~＋ and low CD133~＋. The enriched breast cancer cell spheres exhibited stronger tumorigenicity than adherent cells. DC vaccine prepared with BSC lysates elicited specific T-cell responses against BSC. DC vaccine stimulated Th1 response and induced significant IFN-γ production, which was correlated with the number of activated CTLs. Conclusion The breast cancer cell spheres have stem cell characteristics and strong tumorigenicity. DC inoculation with BSC antigen can elicit effective antigen-specific Th1 response, further activating antigen-specific CTLs and inducing IFN-γ production.