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

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 Dae Han, Suk-Jo Kang, Sang Joon Shin, Yeonseok Chung and Chang-Yuil Kang ()
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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
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

Nature Communications, 2017, vol. 8, issue 1, 1-14

Abstract: 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.

Date: 2017
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DOI: 10.1038/ncomms15776

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