Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, China.
Department of Biotherapy, Sun Yat-sen University Cancer Center, Guangzhou, 510060, People's Republic of China.
Cancer Immunol Immunother. 2020 May;69(5):825-834. doi: 10.1007/s00262-020-02486-y. Epub 2020 Feb 14.
Adjuvant cytokine-induced killer (CIK) cell immunotherapy has shown potential in improving the prognosis of hepatocellular carcinoma (HCC) patients after curative resection. However, whether an individual could obtain survival benefit from CIK cell treatment remains unknown. In the present study, we focused on the characteristics of CIK cells and aimed to identify the best predictive biomarker for adjuvant CIK cell treatment in patients with HCC after surgery. This study included 48 patients with HCC treated with postoperative adjuvant CIK cell immunotherapy. The phenotype activity and cytotoxic activity of CIK cells were determined by flow cytometry and xCELLigence™ Real-Time Cell Analysis (RTCA) system, respectively. Correlation analysis revealed that the cytotoxic activity of CIK cells was significantly negative correlated with the percentage of CD3+ CD4+ cell subsets, but significantly positive correlated with CD3-CD56+ and CD3+ CD56+ cell subsets. Survival analysis showed that there were no significant associations between patients' prognosis and the phenotype of CIK cells. By contrast, there was statistically significant improvement in recurrence-free survival (RFS) and overall survival (OS) for patients with high cytotoxic activity of CIK cells as compared with those with low cytotoxic activity of CIK cells. Univariate and multivariate analyses indicated that CIK cell cytotoxicity was an independent prognostic factor for RFS and OS. In conclusion, a high cytotoxic activity of CIK cells can serve as a valuable biomarker for adjuvant CIK cell immunotherapy of HCC patients after surgery.
辅助细胞因子诱导的杀伤(CIK)细胞免疫疗法已显示出改善肝癌(HCC)患者根治性切除术后预后的潜力。然而,个体是否能从 CIK 细胞治疗中获得生存获益尚不清楚。在本研究中,我们专注于 CIK 细胞的特征,并旨在确定用于术后 HCC 患者辅助 CIK 细胞治疗的最佳预测生物标志物。本研究纳入了 48 例接受术后辅助 CIK 细胞免疫治疗的 HCC 患者。通过流式细胞术和 xCELLigence™实时细胞分析(RTCA)系统分别确定 CIK 细胞的表型活性和细胞毒性活性。相关性分析表明,CIK 细胞的细胞毒性活性与 CD3+CD4+细胞亚群的百分比呈显著负相关,但与 CD3-CD56+和 CD3+CD56+细胞亚群呈显著正相关。生存分析表明,患者的预后与 CIK 细胞的表型之间没有显著关联。相比之下,与 CIK 细胞低细胞毒性活性的患者相比,CIK 细胞具有高细胞毒性活性的患者的无复发生存率(RFS)和总生存率(OS)显著提高。单因素和多因素分析表明,CIK 细胞细胞毒性是 RFS 和 OS 的独立预后因素。总之,CIK 细胞的高细胞毒性可以作为 HCC 患者术后辅助 CIK 细胞免疫治疗的有价值的生物标志物。