title: Interleukin-28B acts synergistically with cisplatin to suppress the growth of head and neck squamous cell carcinoma.
abstract: Interleukin-28B (IL-28B), also referred to as interferon-λ3, belongs to the type III interferon family. Earlier studies showed that IL-28B suppresses proliferation of some tumor cells in vitro. IL-28B gene transfection ex vivo also resulted in growth retardation of tumor cells in mice, through either direct antiproliferative action or induction of antitumor immunity. However, it has not been reported whether in vivo therapeutic administration of recombinant IL-28B can inhibit the growth of a pre-established tumor. Here, we found that repetitive subcutaneous administration of recombinant mouse IL-28B significantly induced tumor-specific cytotoxic T lymphocytes and augmented natural killer cytolytic activity, leading to moderate suppression of the growth of a murine head and neck squamous cell carcinoma (HNSCC) cell line that was completely resistant to the direct antiproliferative effect of IL-28B. Moreover, co-administration of recombinant mouse IL-28B and cisplatin (CDDP) more significantly inhibited in vivo growth of the tumor that had been established in syngenic mice and induced tumor-specific cytotoxic T lymphocytes. The CDDP treatment induced the expression of major histocompatibility complex class I and Fas molecules on the surface of HNSCC cells both in vitro and in vivo; this may be the mechanism underlying the synergistic tumor suppression activity of IL-28B and CDDP. Unlike type I interferon, IL-28B did not suppress growth of bone marrow cells in culture. Therefore, IL-28B may be useful as a tool for a novel multidisciplinary therapy against cancer, significantly potentiating innate and adaptive antitumor immune responses, especially when co-administrated with CDDP, which is currently the first choice chemotherapeutic agent against various tumors including HNSCCs.
authors.affiliation: Department of Otorhinolaryngology-Head and Neck Surgery, Kyoto Prefectural University of Medicine, Faculty of Life Science, Kyoto Sangyo University, Kyoto, Japan.
authors.forename: Koichiro
authors.initials: K
authors.lastname: Yoshimoto
authors.forename: Tsunao
authors.initials: T
authors.lastname: Kishida
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nakano
authors.forename: Masahiro
authors.initials: M
authors.lastname: Matsui
authors.forename: Masaharu
authors.initials: M
authors.lastname: Shin-Ya
authors.forename: Taketoshi
authors.initials: T
authors.lastname: Shimada
authors.forename: Shigeru
authors.initials: S
authors.lastname: Nakai
authors.forename: Jiro
authors.initials: J
authors.lastname: Imanishi
authors.forename: Minoru
authors.initials: M
authors.lastname: Takeuchi
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Hisa
authors.forename: Osam
authors.initials: O
authors.lastname: Mazda
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology / Q000627:therapeutic use; D004357:Drug Synergism; D005260:Female; D006183:H-2 Antigens / Q000378:metabolism; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000276:immunology; D007378:Interleukins / Q000494:pharmacology / Q000627:therapeutic use; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology; D008546:Melanoma, Experimental / Q000188:drug therapy; D051379:Mice; D008809:Mice, Inbred C3H; D018307:Neoplasms, Squamous Cell / Q000188:drug therapy* / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000276:immunology; D023041:Xenograft Model Antitumor Assays; D019014:fas Receptor / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D006183:H-2 Antigens; D007378:Interleukins; D019014:fas Receptor; D002945:Cisplatin