Immunophenotype and antitumor activity of cytokine-induced killer cells from patients with hepatocellular carcinoma

Chan Keng Yang, Chien Hao Huang, Ching Hsun Hu, Jian He Fang, Tse-Ching Chen, Yung Chang Lin*, Chun Yen Lin

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

2 Scopus citations


Background Cytokine-induced killer (CIK) cells are heterogeneous lymphocytes from human peripheral blood mononucleated cells (PBMCs) co-cultured with several cytokines. The main purpose of this study is to evaluate the functional characteristics and anticancer ability of CIK cells from hepatocarcinoma (HCC) patients. Methods CIK cells were activated ex-vivo and expanded from PBMCs from HCC patients. The immunophenotype and the ex-vivo killing ability of CIK cells were evaluated. Human CIK cells were intravenously injected into NOD/SCID mice to evaluate the in vivo anticancer ability. Results More than 70% of CIK cells were CD3+CD8+, and 15%–30% were CD3+CD56+. These cells expressed an increased number of activated natural killer (NK) receptors, such as DNAM1 and NKG2D, and expressed low-immune checkpoint molecules, including PD-1, CTLA-4, and LAG-3. Among the chemokine receptors expressed by CIKs, CXCR3 and CD62L were elevated in CD8+ T cells, representing the trafficking ability to inflamed tumor sites. CIK cells possess the ex-vivo anticancer activity to different cell lines. To demonstrate in vivo antitumor ability, human CIK cells could significantly suppress the tumor of J7 bearing NOD/SCID mice. Furthermore, human immune cells could be detected in the peripheral blood and on the tumors after CIK injection. Conclusions This study revealed that CIK cells from HCC patients possess cytotoxic properties, and express increased levels of effector NK receptors and chemokine molecules and lower levels of suppressive checkpoint receptors. CIK cells can suppress human HCC ex-vivo and in vivo. Future clinical trials of human CIK cell therapy for HCC are warranted.

Original languageEnglish
Article numbere0280023
Pages (from-to)e0280023
JournalPLoS ONE
Issue number1
StatePublished - 01 2023

Bibliographical note

Copyright: © 2023 Yang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


  • Animals
  • Mice
  • Humans
  • Carcinoma, Hepatocellular/pathology
  • Cytokine-Induced Killer Cells/pathology
  • Liver Neoplasms/pathology
  • Mice, SCID
  • Mice, Inbred NOD
  • Cytokines/pharmacology
  • Cytotoxicity, Immunologic


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