FOXP3 Inhibitory Peptide P60 Increases Efficacy of Cytokine-induced Killer Cells Against Renal and Pancreatic Cancer Cells

Anticancer Res. 2019 Oct;39(10):5369-5374. doi: 10.21873/anticanres.13730.

Abstract

Background/aim: Cytokine-induced killer (CIK) cells are ex vivo expanded major histocompatibility complex (MHC)-unrestricted cytotoxic cells with promising effects against a variety of cancer types. Regulatory T-cells (T-reg) have been shown to reduce the effectiveness of CIK cells against tumor cells. Peptide P60 has been shown to inhibit the immunosuppressive functions of T-regs. This study aimed at examining the effect of p60 on CIK cells efficacy against renal and pancreatic cancer cells.

Materials and methods: The effect of P60 on CIK cytotoxicity was examined using flow cytometry, WST-8-based cell viability assay and interferon γ (IFNγ) ELISA.

Results: P60 treatment resulted in a significant decrease in the viability of renal and pancreatic cancer cell lines co-cultured with CIK cells. No increase in IFNγ secretion from CIK cells was detected following treatment with P60. P60 caused no changes in the distribution of major effector cell populations in CIK cell cultures.

Conclusion: P60 may potentiate CIK cell cytotoxicity against tumor cells.

Keywords: Cytokine-induced killer (CIK) cells; FOXP3; adoptive cell transfer; cancer; immunotherapy.

MeSH terms

  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Coculture Techniques / methods
  • Cytokine-Induced Killer Cells / drug effects*
  • Cytokine-Induced Killer Cells / metabolism
  • Cytokines / metabolism*
  • Cytotoxicity, Immunologic / drug effects
  • Forkhead Transcription Factors / antagonists & inhibitors*
  • Humans
  • Interferon-gamma / metabolism
  • Kidney / drug effects
  • Kidney / metabolism
  • Kidney Neoplasms / drug therapy*
  • Kidney Neoplasms / metabolism
  • Pancreas / drug effects
  • Pancreas / metabolism
  • Pancreatic Neoplasms / drug therapy*
  • Pancreatic Neoplasms / metabolism
  • Peptides / pharmacology*
  • T-Lymphocytes, Regulatory / drug effects
  • T-Lymphocytes, Regulatory / metabolism

Substances

  • Cytokines
  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • Peptides
  • Interferon-gamma