Minimally invasive treatment combined with cytokine-induced killer cells therapy lower the short-term recurrence rates of hepatocellular carcinomas

J Immunother. 2008 Jan;31(1):63-71. doi: 10.1097/CJI.0b013e31815a121b.

Abstract

The recurrence of hepatocellular carcinoma (HCC) after minimally invasive therapy is frequent. Adoptive immunotherapy is thought to be an effective method to lower recurrence and metastasis rates of malignant tumors. Therefore, 85 HCC patients after transcatheter arterial chemoembolization and radiofrequency ablation therapy were randomized to immunotherapy group and no adjuvant therapy group. Autologous cytokine-induced killer (CIK) cells were transfused via hepatic artery to the patients. The alteration of levels of lymphocyte subsets in peripheral blood of patients was examined by flow cytometry. All patients were screened by computed tomography every 2 months to observe the tumor recurrent conditions. After CIK cell infusions, the percentages of CD3+, CD4+, CD56+, CD3+CD56+ cells, and CD4+/CD8+ ratio increased from 68.6+/-11.0%, 31.1+/-9.0%, 15.6+/-7.9%, 5.2+/-3.1%, and 1.1+/-0.5 to 70.7+/-10.1%, 33.5+/-8.0%, 18.4+/-9.4%, 5.9+/-2.8%, and 1.3+/-0.7, respectively (P<0.05); whereas the percentage of CD8 cells decreased from 31.1+/-7.8% to 28.6+/-8.3% (P<0.05). The 1-year and 18-month recurrence rates of the study group were 8.9% and 15.6%, compared with 30.0% and 40.0% of the control group (both P value<0.05). The data suggest that CIK cell transfusion is an effective treatment. It can boost the immunologic function in HCC patients and plays an important role in reducing the recurrence rate of HCC.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • CD3 Complex / analysis
  • CD56 Antigen / analysis
  • CD8 Antigens / analysis
  • Carcinoma, Hepatocellular / pathology
  • Carcinoma, Hepatocellular / therapy*
  • Cell Line, Tumor
  • Combined Modality Therapy
  • Cytotoxicity Tests, Immunologic
  • Female
  • Humans
  • Immunophenotyping
  • Immunotherapy, Adoptive / methods*
  • Interferon-gamma / metabolism
  • Interleukin-4 / metabolism
  • Killer Cells, Lymphokine-Activated / immunology
  • Killer Cells, Lymphokine-Activated / metabolism
  • Killer Cells, Lymphokine-Activated / transplantation*
  • Leukocytes, Mononuclear / chemistry
  • Leukocytes, Mononuclear / immunology
  • Liver Neoplasms / pathology
  • Liver Neoplasms / therapy*
  • Lymphocyte Subsets / immunology
  • Lymphocyte Subsets / metabolism
  • Lymphocyte Subsets / transplantation*
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local / prevention & control*
  • Treatment Outcome

Substances

  • CD3 Complex
  • CD56 Antigen
  • CD8 Antigens
  • IL4 protein, human
  • Interleukin-4
  • Interferon-gamma