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Stem Cell Reports. 2016 Feb 9;6(2):213-27. doi: 10.1016/j.stemcr.2016.01.005.

Cellular Adjuvant Properties, Direct Cytotoxicity of Re-differentiated Vα24 Invariant NKT-like Cells from Human Induced Pluripotent Stem Cells.

Author information

1
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.
2
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.
3
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.
4
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.
5
Division of Immunology, Aichi Cancer Center Research Institute (ACCRI), 1-1 Kanokoden, Chikusa-ku, Nagoya, Aichi 464-8681, Japan.
6
Sequencing Core Facility, CiRA, Kyoto University, 53 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8501, Japan.
7
Division of Cancer Immunotherapy, Exploratory Oncology Research & Clinical Trial Center, National Cancer Center (NCC), 6-5-1 Kashiwanoha, Kashiwa, Chiba 277-8577, Japan.
8
Research Center for Stem Cell Engineering, National Institute of Advanced Industrial Science and Technology (AIST), 1-1-1 Higashi, Tsukuba, Ibaraki 305-8561, Japan.
9
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.
10
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.

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.

PMID:
26862702
PMCID:
PMC4750166
DOI:
10.1016/j.stemcr.2016.01.005
[Indexed for MEDLINE]
Free PMC Article

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