CIK cell cytotoxicity is a predictive biomarker for CIK cell immunotherapy in postoperative patients with hepatocellular carcinoma
CIK cell cytotoxicity is a predictive biomarker for CIK cell immunotherapy in postoperative patients with hepatocellular carcinoma
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CIK细胞的细胞毒性是肝细胞癌术后CIK细胞免疫治疗的预测生物标志物
DOI：
10.1007/s00262-020-02486-y
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发表时间：
2020-02-14
影响因子：
5.8
通讯作者：
Xia, Jian-Chuan
中科院分区：
文献类型：
--
作者：
Pan, Qiu-Zhong;Liu, Qing;Xia, Jian-Chuan
辅助细胞因子诱导杀伤（CIK）细胞免疫治疗已显示出改善肝细胞癌（HCC）患者根治性切除后预后的潜力。然而，个体是否能够从 CIK 细胞治疗中获得生存获益仍然未知。在本研究中，我们重点关注 CIK 细胞的特征，旨在确定 HCC 患者术后辅助 CIK 细胞治疗的最佳预测生物标志物。这项研究包括 48 名接受术后辅助 CIK 细胞免疫治疗的 HCC 患者。 CIK细胞的表型活性和细胞毒活性分别通过流式细胞术和xCELLigence™实时细胞分析（RTCA）系统测定。相关分析显示，CIK细胞的细胞毒活性与CD3+ CD4+ 细胞亚群百分比呈显着负相关，与CD3-CD56+ 和CD3+ CD56+ 细胞亚群百分比显着正相关。生存分析显示，患者的预后与CIK细胞的表型之间没有显着相关性。相比之下，与CIK细胞低细胞毒活性的患者相比，CIK细胞高细胞毒活性的患者的无复发生存期（RFS）和总生存期（OS）有统计学上显着的改善。单变量和多变量分析表明 CIK 细胞的细胞毒性是 RFS 和 OS 的独立预后因素。总之，CIK细胞的高细胞毒活性可以作为HCC患者术后辅助CIK细胞免疫治疗的有价值的生物标志物。
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.