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Interferon-alpha promotes immunosuppression through IFNAR1/STAT1 signalling in head and neck squamous cell carcinoma
BACKGROUND: An immunosuppressive microenvironment is critical for cancer initiation and progression. Whether interferon alpha (IFNα) can suppress immune and cancer cells and its involved mechanism still remain largely elusive. METHODS: We examine the expression of interferon alpha/beta receptor-1 (I...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6353953/ https://www.ncbi.nlm.nih.gov/pubmed/30555157 http://dx.doi.org/10.1038/s41416-018-0352-y |
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author | Ma, Hailong Yang, Wenyi Zhang, Liming Liu, Shuli Zhao, Mei Zhou, Ge Wang, Lizhen Jin, Shufang Zhang, Zhiyuan Hu, Jingzhou |
author_facet | Ma, Hailong Yang, Wenyi Zhang, Liming Liu, Shuli Zhao, Mei Zhou, Ge Wang, Lizhen Jin, Shufang Zhang, Zhiyuan Hu, Jingzhou |
author_sort | Ma, Hailong |
collection | PubMed |
description | BACKGROUND: An immunosuppressive microenvironment is critical for cancer initiation and progression. Whether interferon alpha (IFNα) can suppress immune and cancer cells and its involved mechanism still remain largely elusive. METHODS: We examine the expression of interferon alpha/beta receptor-1 (IFNAR1), CD8, CD56 and programmed death ligand 1 (PDL1) in head and neck squamous cell carcinomas (HNSCC). The effect of IFNα on PDL1 and programmed cell death protein 1 (PD1) expression in tumour cells and immune cells was detected in vitro and in vivo. RESULTS: Overexpression of IFNAR1, MX1 and signal transducer and activator of transcription 1 (Stat1) indicated the endogenous IFNα activation in tumour microenvironment, which correlated with immunosuppression status in HNSCC patients. Moreover, IFNα transcriptionally activated the expression of PDL1 through p-Stat1 (Tyr701) and promoted PD1 expression in immune cells through IFNAR1. The inhibition of IFNα signalling enhanced the cytotoxic activity of nature killer cells. At lastastly, we confirmed the upregulation of PDL1 and PD1 in response to IFNα treatment in both xenograft tumour models and patient-derived xenograft models. CONCLUSIONS: Our findings demonstrate that IFNα-induced PDL1 and PD1 expression is a new mechanism of immunosuppression in HNSCC, suggesting that blocking IFNα signalling may enhance the efficacy of immune checkpoint blockade. |
format | Online Article Text |
id | pubmed-6353953 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-63539532019-12-17 Interferon-alpha promotes immunosuppression through IFNAR1/STAT1 signalling in head and neck squamous cell carcinoma Ma, Hailong Yang, Wenyi Zhang, Liming Liu, Shuli Zhao, Mei Zhou, Ge Wang, Lizhen Jin, Shufang Zhang, Zhiyuan Hu, Jingzhou Br J Cancer Article BACKGROUND: An immunosuppressive microenvironment is critical for cancer initiation and progression. Whether interferon alpha (IFNα) can suppress immune and cancer cells and its involved mechanism still remain largely elusive. METHODS: We examine the expression of interferon alpha/beta receptor-1 (IFNAR1), CD8, CD56 and programmed death ligand 1 (PDL1) in head and neck squamous cell carcinomas (HNSCC). The effect of IFNα on PDL1 and programmed cell death protein 1 (PD1) expression in tumour cells and immune cells was detected in vitro and in vivo. RESULTS: Overexpression of IFNAR1, MX1 and signal transducer and activator of transcription 1 (Stat1) indicated the endogenous IFNα activation in tumour microenvironment, which correlated with immunosuppression status in HNSCC patients. Moreover, IFNα transcriptionally activated the expression of PDL1 through p-Stat1 (Tyr701) and promoted PD1 expression in immune cells through IFNAR1. The inhibition of IFNα signalling enhanced the cytotoxic activity of nature killer cells. At lastastly, we confirmed the upregulation of PDL1 and PD1 in response to IFNα treatment in both xenograft tumour models and patient-derived xenograft models. CONCLUSIONS: Our findings demonstrate that IFNα-induced PDL1 and PD1 expression is a new mechanism of immunosuppression in HNSCC, suggesting that blocking IFNα signalling may enhance the efficacy of immune checkpoint blockade. Nature Publishing Group UK 2018-12-17 2019-02-05 /pmc/articles/PMC6353953/ /pubmed/30555157 http://dx.doi.org/10.1038/s41416-018-0352-y Text en © Cancer Research UK 2018 https://creativecommons.org/licenses/by/4.0/This work is published under the standard license to publish agreement. After 12 months the work will become freely available and the license terms will switch to a Creative Commons Attribution 4.0 International (CC BY 4.0). |
spellingShingle | Article Ma, Hailong Yang, Wenyi Zhang, Liming Liu, Shuli Zhao, Mei Zhou, Ge Wang, Lizhen Jin, Shufang Zhang, Zhiyuan Hu, Jingzhou Interferon-alpha promotes immunosuppression through IFNAR1/STAT1 signalling in head and neck squamous cell carcinoma |
title | Interferon-alpha promotes immunosuppression through IFNAR1/STAT1 signalling in head and neck squamous cell carcinoma |
title_full | Interferon-alpha promotes immunosuppression through IFNAR1/STAT1 signalling in head and neck squamous cell carcinoma |
title_fullStr | Interferon-alpha promotes immunosuppression through IFNAR1/STAT1 signalling in head and neck squamous cell carcinoma |
title_full_unstemmed | Interferon-alpha promotes immunosuppression through IFNAR1/STAT1 signalling in head and neck squamous cell carcinoma |
title_short | Interferon-alpha promotes immunosuppression through IFNAR1/STAT1 signalling in head and neck squamous cell carcinoma |
title_sort | interferon-alpha promotes immunosuppression through ifnar1/stat1 signalling in head and neck squamous cell carcinoma |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6353953/ https://www.ncbi.nlm.nih.gov/pubmed/30555157 http://dx.doi.org/10.1038/s41416-018-0352-y |
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