我们发现人原发性肝癌(HCC)浸润的特异性杀伤性T细胞(CTL)处于衰老状态并高表达衰老分子Tim-3、PD-1，阻断上述分子后发现CTL功能部分恢复但抗肿瘤效果仍欠佳。最近表明，将外周血T细胞重编程为诱导多能干细胞(iPSC)并再分化为T细胞，可在保留抗原特异性情况下使T细胞彻底“年轻化”。我们预实验将HCC-CTL重编程为T-iPSC，但其是否携带来源T细胞受体(TCR)基因及再分化为年轻化CTL的能力尚待验证。本课题在干细胞分化、抗HCC研究等基础上，拟：1.将HCC-CTL重编程为T-iPSC然后再分化为CTL，并检测其增殖能力提高、免疫活性增强等年轻化特征及高效特异性杀伤HCC情况；2.研究其中通过染色体端粒延长、端粒酶活性增强而使细胞年轻化的机制，通过保持TCR基因遗传稳定而保留其抗原特异性的机制。本课题旨在获得年轻化CTL用于HCC治疗，并促进肿瘤的干细胞治疗机制完善和更新。

We have found that most of cytotoxic T cells (CTLs) in tumor of hepatocellular carcinoma (HCC) patients are at the state of senescence and high expression of inhibitory receptors such as T cell immunoglobulin and mucin domain–containing molecule 3 (Tim-3) and programmed death 1(PD-1), when blocked both of them, the function of CTLs can be restored to some extent, while the anti-tumor effect of them is still poor. Recently, we found that T cells can be reprogrammed into induced pluripotent stem cells (iPSCs) and then redifferentiated into CTLs which called “rejuvenated”cells possessed antigen-specific killing activity. We had got the CTL - iPSCs, but whether they owned the same T cell receptor (TCR) gene with CTLs and their capacity of proliferation is yet to be further verified.Therefore, our research will carry out the following works: Firstly, we reprogrammed HCC-CTLs into T-iPSCs and redifferentiated them into CTLs, then detect cell proliferation, activity and whether they carry the same TCR gene with HCC-CTLs. Secondly, we explore the mechanisms of generatin of rejuvenated iPSCs-CTLs as well as the mechanisms of genetic stability of TCR genes. Our research aims to get rejuvenated CTLs for HCC treatment and improve the development of stem cell technology.