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Isolation and Expansion of Cytotoxic Cytokine-induced Killer T Cells for Cancer Treatment
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Multiple cytotoxic factors involved in IL-21 enhanced antitumor function of CIK cells signaled through STAT-3 and

S Rajbhandary1, Ming-Feng Zhao, Nan Zhao

  • 1Department of Hematology, Tianjin First Central Hospital, Tianjin, China

Asian Pacific Journal of Cancer Prevention : APJCP
|December 3, 2013
PubMed
Abstract

Insights

Interleukin-21 (IL-21) enhances the cytotoxic potential of cytokine-induced killer (CIK) cells by increasing key cytotoxic factors, mediated through the STAT-3 and STAT-5b signaling pathways.

Area of Science:

  • Immunology
  • Cell Biology
  • Cancer Therapy

Background:

  • Adoptive immunotherapy relies on maintaining cellular function in culture.
  • Interleukin-21 (IL-21) has dual properties: T cell activation and reduction of cell death.

Purpose of the Study:

  • To explore the mechanism by which IL-21 enhances the proliferation and cytotoxic potential of cytokine-induced killer (CIK) cells.

Main Methods:

  • CIK cells were stimulated with IL-21.
  • Cellular viability and cytotoxicity were measured.
  • mRNA and protein expression of cytotoxic factors were assessed via RT-PCR, flow cytometry, and ELISA.
  • JAK/STAT pathway involvement was analyzed by Western blotting.

Main Results:

  • IL-21 did not enhance CIK cell proliferation but increased CD3+/CD56+ phenotype expression.
  • Cytotoxic potential increased, with significant upregulation of perforin, granzyme B, and FasL.
  • Interferon-gamma and TNF-alpha levels increased significantly.
  • IL-21 signaling involved the STAT-3 and STAT-5b pathways.

Conclusions:

  • IL-21 enhances CIK cell cytotoxic potential by upregulating perforin, granzyme B, IFN-gamma, and TNF-alpha.
  • This enhancement is mediated by the activation of STAT-3 and STAT-5b proteins.

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