High number of PD-1 positive intratumoural lymphocytes predicts survival benefit of cytokine-induced killer cells for hepatocellular carcinoma patients

Liver Int. 2018 Aug;38(8):1449-1458. doi: 10.1111/liv.13697. Epub 2018 Feb 13.


Background & aims: Adjuvant cytokine-induced killer (CIK) cells treatment has shown potential in reducing the recurrence rate and prolonging the survival of patients with hepatocellular carcinoma (HCC). We aimed to identify the best predictive biomarker for adjuvant CIK cells treatment in patients with HCC after curative resection.

Methods: This study retrospectively included 145 pairs of HCC patients by one-to-one propensity score matching. One group received CIK cells transfusion after surgery (surgery-CIK group); the other one group underwent surgery only (surgery-only group). Immunohistochemistry (IHC) was used to measure PD-1, PD-L1, CD4, CD8 and Foxp3 expression in tumour tissues of surgery-CIK group; IHC of PD-1 and PD-L1 was conducted in the surgery-only group.

Results: The surgery-CIK group had a significantly higher disease-free survival (DFS) and overall survival (OS) rates compared to the surgery-only group. Of all the intratumoural biomarkers, in the surgery-CIK group, multivariate analysis showed that a high number of PD-1+ tumour infiltrative lymphocytes (TILs) was the only factor that independently predicted favourable OS and DFS. By contrast, in the surgery-only group, no significant correlations between PD-1/PD-L1 expression and survival of patients were identified. Further correlation analysis showed a high number of PD-1+ TILs associated with a high number of both CD4+ and CD8+ TILs in surgery-CIK group.

Conclusions: A high number of PD-1+ TILs can serve as a potent biomarker for adopting CIK cells therapy in HCC patients after curative resection.

Keywords: adoptive cellular immunotherapy; cancer; immunohistochemistry; prognosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / immunology
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / metabolism
  • Carcinoma, Hepatocellular / mortality
  • Carcinoma, Hepatocellular / therapy*
  • China / epidemiology
  • Combined Modality Therapy
  • Cytokine-Induced Killer Cells / transplantation*
  • Female
  • Hepatectomy
  • Humans
  • Immunohistochemistry
  • Immunotherapy*
  • Liver Neoplasms / mortality
  • Liver Neoplasms / therapy*
  • Lymphocytes, Tumor-Infiltrating / immunology
  • Lymphocytes, Tumor-Infiltrating / metabolism
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Programmed Cell Death 1 Receptor / immunology*
  • Propensity Score
  • Retrospective Studies
  • Survival Analysis


  • Biomarkers, Tumor
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor