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

Cancer Immunol Immunother. 2020 May;69(5):825-834. doi: 10.1007/s00262-020-02486-y. Epub 2020 Feb 14.

Abstract

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.

Keywords: CIK cell immunotherapy; Cytotoxicity; Hepatocellular carcinoma; Prognosis.

MeSH terms

  • Carcinoma, Hepatocellular / immunology
  • Carcinoma, Hepatocellular / mortality
  • Carcinoma, Hepatocellular / therapy*
  • Cell Culture Techniques
  • Cells, Cultured / immunology
  • Cells, Cultured / transplantation
  • Combined Modality Therapy / methods
  • Cytokine-Induced Killer Cells / immunology
  • Cytokine-Induced Killer Cells / transplantation*
  • Cytotoxicity Tests, Immunologic
  • Cytotoxicity, Immunologic*
  • Female
  • Flow Cytometry
  • Hepatectomy
  • Humans
  • Immunotherapy / methods*
  • Liver Neoplasms / immunology
  • Liver Neoplasms / mortality
  • Liver Neoplasms / therapy*
  • Male
  • Middle Aged
  • Postoperative Period
  • Prognosis
  • Survival Analysis
  • Transplantation, Autologous / methods