title: Cellular Adjuvant Properties, Direct Cytotoxicity of Re-differentiated Vα24 Invariant NKT-like Cells from Human Induced Pluripotent Stem Cells.
abstract: Vα24 invariant natural killer T (iNKT) cells are a subset of T lymphocytes implicated in the regulation of broad immune responses. They recognize lipid antigens presented by CD1d on antigen-presenting cells and induce both innate and adaptive immune responses, which enhance effective immunity against cancer. Conversely, reduced iNKT cell numbers and function have been observed in many patients with cancer. To recover these numbers, we reprogrammed human iNKT cells to pluripotency and then re-differentiated them into regenerated iNKT cells in vitro through an IL-7/IL-15-based optimized cytokine combination. The re-differentiated iNKT cells showed proliferation and IFN-γ production in response to α-galactosylceramide, induced dendritic cell maturation and downstream activation of both cytotoxic T lymphocytes and NK cells, and exhibited NKG2D- and DNAM-1-mediated NK cell-like cytotoxicity against cancer cell lines. The immunological features of re-differentiated iNKT cells and their unlimited availability from induced pluripotent stem cells offer a potentially effective immunotherapy against cancer.
authors: Shin Kaneko Laboratory, Department of Cell Growth and Differentiation, Center for iPS Cell Research and Application (CiRA), Kyoto University, 53 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8501, Japan.
authors: Shuichi
authors: S
authors: Kitayama
authors: Division of Immunology, Aichi Cancer Center Research Institute (ACCRI), 1-1 Kanokoden, Chikusa-ku, Nagoya, Aichi 464-8681, Japan; Division of Cancer Immunotherapy, Exploratory Oncology Research & Clinical Trial Center, National Cancer Center (NCC), 6-5-1 Kashiwanoha, Kashiwa, Chiba 277-8577, Japan.
authors: Rong
authors: R
authors: Zhang
authors: Division of Immunology, Aichi Cancer Center Research Institute (ACCRI), 1-1 Kanokoden, Chikusa-ku, Nagoya, Aichi 464-8681, Japan; Key Laboratory of Cancer Center, Chinese PLA General Hospital, 28 Fuxing Road, Beijing 100853, China.
authors: Tian-Yi
authors: TY
authors: Liu
authors: Shin Kaneko Laboratory, Department of Cell Growth and Differentiation, Center for iPS Cell Research and Application (CiRA), Kyoto University, 53 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8501, Japan; Division of Immunology, Aichi Cancer Center Research Institute (ACCRI), 1-1 Kanokoden, Chikusa-ku, Nagoya, Aichi 464-8681, Japan.
authors: Norihiro
authors: N
authors: Ueda
authors: Shin Kaneko Laboratory, Department of Cell Growth and Differentiation, Center for iPS Cell Research and Application (CiRA), Kyoto University, 53 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8501, Japan.
authors: Shoichi
authors: S
authors: Iriguchi
authors: Shin Kaneko Laboratory, Department of Cell Growth and Differentiation, Center for iPS Cell Research and Application (CiRA), Kyoto University, 53 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8501, Japan.
authors: Yutaka
authors: Y
authors: Yasui
authors: Shin Kaneko Laboratory, Department of Cell Growth and Differentiation, Center for iPS Cell Research and Application (CiRA), Kyoto University, 53 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8501, Japan.
authors: Yohei
authors: Y
authors: Kawai
authors: Division of Immunology, Aichi Cancer Center Research Institute (ACCRI), 1-1 Kanokoden, Chikusa-ku, Nagoya, Aichi 464-8681, Japan.
authors: Minako
authors: M
authors: Tatsumi
authors: Shin Kaneko Laboratory, Department of Cell Growth and Differentiation, Center for iPS Cell Research and Application (CiRA), Kyoto University, 53 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8501, Japan.
authors: Norihito
authors: N
authors: Hirai
authors: Sequencing Core Facility, CiRA, Kyoto University, 53 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8501, Japan.
authors: Yasutaka
authors: Y
authors: Mizoro
authors: Division of Cancer Immunotherapy, Exploratory Oncology Research & Clinical Trial Center, National Cancer Center (NCC), 6-5-1 Kashiwanoha, Kashiwa, Chiba 277-8577, Japan.
authors: Tatsuaki
authors: T
authors: Iwama
authors: Sequencing Core Facility, CiRA, Kyoto University, 53 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8501, Japan.
authors: Akira
authors: A
authors: Watanabe
authors: Research Center for Stem Cell Engineering, National Institute of Advanced Industrial Science and Technology (AIST), 1-1-1 Higashi, Tsukuba, Ibaraki 305-8561, Japan.
authors: Mahito
authors: M
authors: Nakanishi
authors: Division of Immunology, Aichi Cancer Center Research Institute (ACCRI), 1-1 Kanokoden, Chikusa-ku, Nagoya, Aichi 464-8681, Japan.
authors: Kiyotaka
authors: K
authors: Kuzushima
authors: Division of Immunology, Aichi Cancer Center Research Institute (ACCRI), 1-1 Kanokoden, Chikusa-ku, Nagoya, Aichi 464-8681, Japan; Division of Cancer Immunotherapy, Exploratory Oncology Research & Clinical Trial Center, National Cancer Center (NCC), 6-5-1 Kashiwanoha, Kashiwa, Chiba 277-8577, Japan. Electronic address: yuemura@east.ncc.go.jp.
authors: Yasushi
authors: Y
authors: Uemura
authors: Shin Kaneko Laboratory, Department of Cell Growth and Differentiation, Center for iPS Cell Research and Application (CiRA), Kyoto University, 53 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8501, Japan. Electronic address: kaneko.shin@cira.kyoto-u.ac.jp.
authors: Shin
authors: S
authors: Kaneko
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects*; D002460:Cell Line; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology* / Q000187:drug effects; D007694:Killer Cells, Natural / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*
chemical_list: D000276:Adjuvants, Immunologic; D011948:Receptors, Antigen, T-Cell; C528689:Valpha24 protein, human