IL-21-mediated reversal of NK cell exhaustion facilitates anti-tumour immunity in MHC class I-deficient tumours
| Autor: | Jiyoun Min, Sang Joon Shin, Myung Hwan Park, Chang-Yuil Kang, Yeonseok Chung, Ki-Young Choi, Byung Soh Min, Hyungseok Seo, Yoon Dae Han, Choong-Hyun Koh, Boyeong Song, Suk-Jo Kang, Insu Jeon, Il-Kyu Kim, Eun-Ah Bae, Byung-Seok Kim, Taegwon Oh, Kwangsoo Shin |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
medicine.medical_treatment Science Programmed Cell Death 1 Receptor Genes MHC Class I General Physics and Astronomy chemical and pharmacologic phenomena Biology Major histocompatibility complex Cancer Vaccines Article General Biochemistry Genetics and Molecular Biology 03 medical and health sciences Immune system Cancer immunotherapy Downregulation and upregulation MHC class I Biomarkers Tumor medicine Animals Humans Neoplasm Hepatitis A Virus Cellular Receptor 2 Melanoma Mice Inbred BALB C Multidisciplinary Interleukins Cancer General Chemistry medicine.disease Xenograft Model Antitumor Assays Killer Cells Natural Mice Inbred C57BL 030104 developmental biology Urinary Bladder Neoplasms Immunoediting Immunology biology.protein Colorectal Neoplasms |
| Zdroj: | Nature Communications, Vol 8, Iss 1, Pp 1-14 (2017) Nature Communications NATURE COMMUNICATIONS(8) |
| ISSN: | 2041-1723 |
| Popis: | 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. Loss of major histocompatibility complex MHC-I expression contributes to cancer immune evasion. Here, the authors show that, in both mice and humans, MHC-I downregulation is associated with the induction of NK-cell exhaustion and that IL-21 restores NK-cell function and inhibits tumours progression. |
| Databáze: | OpenAIRE |
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