头颈肿瘤来源的ALDH1阳性肿瘤干细胞的T细胞免疫调节特性研究

T cell immunoregulatory properties of ALDH1 positive cancer stem-like cells derived from carcinoma cell lines of the head and neck

目的研究头颈肿瘤来源的乙醛脱氢酶同工1(ALDH1)阳性肿瘤干细胞的T细胞免疫调节特性。方法首先培养头颈肿瘤细胞系(UMSCC-9、UMSCC-11B和UMSCC-47),然后通过PCR、流式细胞仪等相关实验,分析比较头颈肿瘤干细胞来源的ALDH1阳性与ALDH1阴性的两类不同细胞对于预激活T细胞的增殖、活化、凋亡以及其他相关功能的影响。结果与ALDH1阴性细胞比较,由ALDH1阳性细胞培养所得的头颈肿瘤细胞具有更强的肿瘤干细胞特性。头颈肿瘤细胞系(UMSCC-9、UMSCC-11B和UMSCC-47)的ALDH1阳性细胞对T细胞增殖抑制效率明显高于ALDH1阴性细胞,ALDH1阳性细胞共培养的T细胞中的细胞因子干扰素γ(IFN-γ)、白介素2(IL-2)、肿瘤坏死因子α(TNF-α)和活化因子CD69、CD137、CD154均明显低于ALDH1阴性细胞(P均<0.05)。结论与ALDH1阴性细胞比较,ALDH1阳性细胞对T细胞的免疫功能有更强的抑制作用。肿瘤干细胞在宿主免疫反应这一复杂交互作用中扮演了主导地位,且最终使肿瘤细胞实现免疫逃避。

Objective To investigate the T cell immunoregulatory characteristics of ALDH1 positive cancer stem-like cells derived from carcinoma cell lines of the head and neck.Methods Head and neck cancer cell lines(UMSCC-9,UMSCC-11B and UMSCC-47)were cultured,and then the effects of ALDH1 positive cells and ALDH1 negative cells derived from head and neck cancer stem cells on the proliferation,activation,apoptosis and other related functions of preactivated T cells were analyzed and compared by PCR and flow cytometry.Results Compared with ALDH1 negative cells,head and neck cancer cells cultured by ALDH1 positive cells had stronger characteristics of cancer stem cells.ALDH1 positive cells from head and neck cancer cell lines(UMSCC-9,UMSCC-11B and UMSCC-47)had significantly higher inhibition efficiency on T cell proliferation than ALDH1 negative cells.The cytokines IFN-γ,IL-2,TNF-α,CD69,CD137 and CD154 of T cells co-cultured with ALDH1 positive cells were significantly lower than those of ALDH1 negative cells(P<0.05).Conclusion Compared with ALDH1 negative cells,ALDH1 positive cells have stronger inhibitory effect on T lymphocyte immune function.Tumor stem cells play a leading role in the complex interaction of host immune response,and ultimately make tumor cells achieve immune escape.