Induced pluripotent stem cell-conditioned medium suppressed melanoma tumorigenicity through the enhancement of natural-killer cellular immunity

Chang Ting Hsieh, Yung Hung Luo, Chian Shiu Chien, Chieh Hung Wu, Pei Chun Tseng, Shih Hwa Chiou, Yu Chin Lee, Jacqueline Whang-Peng, Yuh Min Chen

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Abstract

Induced pluripotent stem cells (iPSCs) can secrete cytokines that are involved in T-cell development and affect cytotoxic activity. To assess the effect of iPSC-conditioned medium on tumorigenicity, we retrieved splenocytes from B6 mice and cocultured them with or without irradiated B16 melanoma cells, mouse interleukin-2 (mIL-2), or iPSC-conditioned medium. Splenocyte cytotoxicity assays against B16 melanoma cells [as cytotoxic T lymphocyte (CTL) activity] and P815 cells [as natural killer (NK) activity] were performed. IL-10 and interferon-γ concentrations were measured. An in vivo subcutaneous B16 melanoma growth model was performed in B6 mice and treated with iPSC-conditioned medium. The lymphocyte subpopulation depletion test was performed to determine effectors against B16 melanoma cells. We found that unstimulated splenocytes had little cytotoxic activity. Without tumor cells, mIL-2 could augment iPSC-conditioned medium-treated CTL and NK activities (P < 0.01). With irradiated tumor cells, mIL-2 treatment of splenocytes could not enhance CTL or NK activity, but iPSC-conditioned medium could enhance CTL and NK activity (P < 0.001). Irradiated tumor cells induced mice splenocytes to secrete more IL-10, similar to mIL-2 treatment, but not iPSC-conditioned medium treatment. mIL-2 had better efficacy than conditioned medium in inducing splenocyte interferon-γ production. The CTL and NK cell depletion test showed that the immunostimulating effect of iPSC-conditioned medium on splenocytes was through the enhancement of NK cellular activity (P < 0.05). The subcutaneous melanoma growth model showed that B16-bearing mice treated with an iPSC-conditioned medium intraperitoneal injection had a decreased tumor growth rate (P < 0.01). Our study suggests that iPSC-conditioned medium had a protective effect against tumor-induced immunosuppression through the enhancement of host NK cellular activity.

Original languageEnglish
Pages (from-to)153-159
Number of pages7
JournalJournal of Immunotherapy
Volume39
Issue number4
DOIs
Publication statusPublished - Jan 1 2016

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Induced Pluripotent Stem Cells
Conditioned Culture Medium
Cellular Immunity
Melanoma
Cytotoxic T-Lymphocytes
Experimental Melanomas
Interleukin-2
Neoplasms
Natural Killer Cells
Interleukin-10
Interferons
Growth
Lymphocyte Depletion
Lymphocyte Subsets
Intraperitoneal Injections
Immunosuppression
Therapeutics
Cytokines
T-Lymphocytes

Keywords

  • Cytotoxic T cells
  • Induced pluripotent stem cells (iPSCs)
  • Melanoma
  • Natural killer cells

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Pharmacology
  • Cancer Research

Cite this

Induced pluripotent stem cell-conditioned medium suppressed melanoma tumorigenicity through the enhancement of natural-killer cellular immunity. / Hsieh, Chang Ting; Luo, Yung Hung; Chien, Chian Shiu; Wu, Chieh Hung; Tseng, Pei Chun; Chiou, Shih Hwa; Lee, Yu Chin; Whang-Peng, Jacqueline; Chen, Yuh Min.

In: Journal of Immunotherapy, Vol. 39, No. 4, 01.01.2016, p. 153-159.

Research output: Contribution to journalArticle

Hsieh, Chang Ting ; Luo, Yung Hung ; Chien, Chian Shiu ; Wu, Chieh Hung ; Tseng, Pei Chun ; Chiou, Shih Hwa ; Lee, Yu Chin ; Whang-Peng, Jacqueline ; Chen, Yuh Min. / Induced pluripotent stem cell-conditioned medium suppressed melanoma tumorigenicity through the enhancement of natural-killer cellular immunity. In: Journal of Immunotherapy. 2016 ; Vol. 39, No. 4. pp. 153-159.
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