title: Induced Pluripotent Stem Cell-conditioned Medium Suppressed Melanoma Tumorigenicity Through the Enhancement of Natural-Killer Cellular Immunity.
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.
authors.affiliation: Departments of *Chest Medicine ‡Medical Research and Education, Taipei Veterans General Hospital †School of Medicine, National Yang-Ming University §National Yang-Ming University ∥Sijhih Cathay General Hospital ¶Taipei Cancer Center, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan, ROC.
authors.forename: Chang-Ting
authors.initials: CT
authors.lastname: Hsieh
authors.forename: Yung-Hung
authors.initials: YH
authors.lastname: Luo
authors.forename: Chian-Shiu
authors.initials: CS
authors.lastname: Chien
authors.forename: Chieh-Hung
authors.initials: CH
authors.lastname: Wu
authors.forename: Pei-Chun
authors.initials: PC
authors.lastname: Tseng
authors.forename: Shih-Hwa
authors.initials: SH
authors.lastname: Chiou
authors.forename: Yu-Chin
authors.initials: YC
authors.lastname: Lee
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Whang-Peng
authors.forename: Yuh-Min
authors.initials: YM
authors.lastname: Chen
mesh_terms: D000818:Animals; D048708:Cell Growth Processes / Q000187:drug effects; D018920:Coculture Techniques; D045424:Complex Mixtures / Q000008:administration & dosage / Q000494:pharmacology*; D017077:Culture Media, Conditioned / Q000494:pharmacology*; D016207:Cytokines / Q000378:metabolism; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D005260:Female; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000502:physiology*; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects; D008545:Melanoma / Q000276:immunology / Q000628:therapy*; D008546:Melanoma, Experimental; D051379:Mice; D008810:Mice, Inbred C57BL; D012878:Skin Neoplasms / Q000276:immunology / Q000628:therapy*; D019139:Tumor Escape
chemical_list: D045424:Complex Mixtures; D017077:Culture Media, Conditioned; D016207:Cytokines