CIK细胞联合PD-L1单抗对肝癌肿瘤干细胞杀伤作用的研究

Cancer stem cells (CSCs) are a subpopulation cancer cells that responsible for initiating and maintaining cancer, and contribute to cancer recurrence, metastasis and therapeutic resistance. It is an urgent need for more potent and safer approaches to eradicate CSCs for curing cancer. In our previous study, we successfully visualized hepatocellular carcinoma (HCC) CSCs in vitro & vivo with a promoter-reporter strategy and demonstrated that CIK cells have strong cancer-killing activities against HCC CSCs in vitro and vivo. However, intensive research work still needs to be done to improve CIK cell-based cancer therapy. It is reported that programmed death-ligand 1 (PD-L1) could express on CSCs and induce immune escape in some solid tumors including glioma, head and neck squamous cell carcinoma and colorectal cancer. However, the expression of PD-L1 on HCC CSCs is completely unexplored. In this study, we fully investigated the expression of PD-L1 on HCC CSCs in various approaches as well as the effects of the combination of CIK cells and PD-L1 blocking against HCC CSCs.

肿瘤干细胞(CSCs)是肿瘤发生、发展、复发及转移的根源，因此有效的清除CSCs至为关键。我们在前期的研究中利用“启动子-报告基因”策略实现了肝癌CSCs体内外的可视化，并证实CIK细胞在达到一定效靶比的情况下能在体内外有效杀伤肝癌CSCs。目前，如何进一步提高其疗效是研究的热点。新近研究证实，部分肿瘤CSCs可通过PD-L1的表达发生免疫逃逸，包括神经胶质瘤CSCs、头颈鳞癌CSCs及结直肠癌CSCs等。然而，PD-L1在肝癌CSCs上的表达尚未明确，本课题将使用细胞与动物模型，结合肝癌临床标本，从分子、细胞与整体水平研究PD-L1在肝癌CSCs中的表达情况，并探索CIK细胞免疫治疗联合PD-L1单抗在体内外对肝癌CSCs的杀伤效果，为肝癌免疫治疗提供新的思路。

肿瘤干细胞(CSCs)是肿瘤发生、发展、复发及转移的根源，课题组在前期的研究中利用“启动子-报告基因”策略实现了肝癌CSCs体内外的可视化，并证实CIK细胞在达到一定效靶比的情况下能在体内外有效杀伤肝癌CSCs。研究证实部分肿瘤CSCs可通过PD-L1的表达发生免疫逃逸。然而，PD-L1在肝癌CSCs上的表达尚未明确，本课题使用细胞与动物模型，结合肝癌临床标本，从分子、细胞与整体水平证实PD-L1可表达于肝癌CSCs，且CIK细胞免疫治疗联合PD-L1单抗可有效的杀伤肝癌CSCs，为肝癌免疫治疗提供新的思路。此外，肿瘤免疫治疗的疗效取决于免疫微环境，课题组围绕着肿瘤微环境开展了部分工作。基于公共数据库课题组构建了结肠癌诊断模型（dIRS）及预后预测模型（pIRS），结果表明该模型可成功应用于肿瘤诊断及预后预测。同时，课题组发现血小板可抑制肿瘤免疫微环境，通过抗血小板治疗可以改善肿瘤免疫微环境，为今后联合免疫治疗提供新思路。