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IL-21-mediated reversal of NK cell exhaustion facilitates anti-tumour immunity in MHC class I-deficient tumours

Author

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  • Hyungseok Seo

    (Laboratory of Immunology, Graduate School of Convergence Science and Technology, Seoul National University)

  • Insu Jeon

    (Laboratory of Immunology, Graduate School of Convergence Science and Technology, Seoul National University)

  • Byung-Seok Kim

    (Laboratory of Immune Regulation, Research Institute of Pharmaceutical Science, College of Pharmacy, Seoul National University)

  • Myunghwan Park

    (Laboratory of Immunology, Graduate School of Convergence Science and Technology, Seoul National University)

  • Eun-Ah Bae

    (Laboratory of Immunology, Graduate School of Convergence Science and Technology, Seoul National University)

  • Boyeong Song

    (Laboratory of Immunology, Graduate School of Convergence Science and Technology, Seoul National University)

  • Choong-Hyun Koh

    (Laboratory of Immunology, Research Institute of Pharmaceutical Science, College of Pharmacy Seoul National University)

  • Kwang-Soo Shin

    (Laboratory of Immunology, Research Institute of Pharmaceutical Science, College of Pharmacy Seoul National University)

  • Il-Kyu Kim

    (Laboratory of Immunology, Graduate School of Convergence Science and Technology, Seoul National University
    Laboratory of Immunology, Research Institute of Pharmaceutical Science, College of Pharmacy Seoul National University)

  • Kiyoung Choi

    (Cellid, Inc.)

  • Taegwon Oh

    (Cellid, Inc.)

  • Jiyoun Min

    (Korea Advanced Institute of Science and Technology)

  • Byung Soh Min

    (Yonsei University College of Medicine)

  • Yoon Dae Han

    (Yonsei University College of Medicine)

  • Suk-Jo Kang

    (Korea Advanced Institute of Science and Technology)

  • Sang Joon Shin

    (Yonsei University College of Medicine)

  • Yeonseok Chung

    (Laboratory of Immune Regulation, Research Institute of Pharmaceutical Science, College of Pharmacy, Seoul National University)

  • Chang-Yuil Kang

    (Laboratory of Immunology, Graduate School of Convergence Science and Technology, Seoul National University
    Laboratory of Immunology, Research Institute of Pharmaceutical Science, College of Pharmacy Seoul National University
    Cellid, Inc.)

Abstract

During cancer immunoediting, loss of major histocompatibility complex class I (MHC-I) in neoplasm contributes to the evasion of tumours from host immune system. Recent studies have demonstrated that most natural killer (NK) cells that are found in advanced cancers are defective, releasing the malignant MHC-I-deficient tumours from NK-cell-dependent immune control. Here, we show that a natural killer T (NKT)-cell-ligand-loaded tumour-antigen expressing antigen-presenting cell (APC)-based vaccine effectively eradicates these advanced tumours. During this process, we find that the co-expression of Tim-3 and PD-1 marks functionally exhausted NK cells in advanced tumours and that MHC-I downregulation in tumours is closely associated with the induction of NK-cell exhaustion in both tumour-bearing mice and cancer patients. Furthermore, the recovery of NK-cell function by IL-21 is critical for the anti-tumour effects of the vaccine against advanced tumours. These results reveal the process involved in the induction of NK-cell dysfunction in advanced cancers and provide a guidance for the development of strategies for cancer immunotherapy.

Suggested Citation

  • Hyungseok Seo & Insu Jeon & Byung-Seok Kim & Myunghwan Park & Eun-Ah Bae & Boyeong Song & Choong-Hyun Koh & Kwang-Soo Shin & Il-Kyu Kim & Kiyoung Choi & Taegwon Oh & Jiyoun Min & Byung Soh Min & Yoon , 2017. "IL-21-mediated reversal of NK cell exhaustion facilitates anti-tumour immunity in MHC class I-deficient tumours," Nature Communications, Nature, vol. 8(1), pages 1-14, August.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms15776
    DOI: 10.1038/ncomms15776
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