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CIK cell cytotoxicity is a predictive biomarker for CIK cell immunotherapy in postoperative patients with hepatocellular carcinoma


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.

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Cellular index

CIK cells:

Cytokine-induced killer cells


Hepatocellular carcinoma


Overall survival


Recurrence-free survival

RTCA system:

Real-Time Cell Analysis system


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This work was primarily supported by a grant from the National Key Research and Development Program of China (No. 2018YFC1313400), the National Natural Science Foundation of China (No. 81803079; 81402560; 81572865; 81472387), the Guangdong Natural Science Foundation (No. 2018A030310237), and the Guangdong Province Science and Technology Plan Project (No. 2017A020215029).

Author information

QZP and QL: data collection, assembly, and data analysis. YQZ, JJZ, QJW, YQL, JMG, YT, JH, and SPC: cell generation, and data analysis and interpretation. DSW and JCX: designed and directed the overall project. QZP, QL, DSW, and JCX: manuscript writing and final approval of the manuscript. All authors read and approved the manuscript.

Correspondence to De-Sheng Weng or Jian-Chuan Xia.

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The authors declare no conflict of interest.

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The Institutional Review Board of the Sun Yat-sen University Cancer Center approved the study design (B2016-035-01). All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

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Informed consent was obtained from all individual participants included in the study.

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Pan, Q., Liu, Q., Zhou, Y. et al. CIK cell cytotoxicity is a predictive biomarker for CIK cell immunotherapy in postoperative patients with hepatocellular carcinoma. Cancer Immunol Immunother (2020). https://doi.org/10.1007/s00262-020-02486-y

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  • CIK cell immunotherapy
  • Hepatocellular carcinoma
  • Cytotoxicity
  • Prognosis