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Tumour-associated neutrophils orchestrate intratumoural IL-8-driven immune evasion through Jagged2 activation in ovarian cancer
BACKGROUND: Tumour associated neutrophils (TANs) play a controversial role in regulating immune surveillance and immune evasion in various malignancies. Here, we investigated the relevance of TANs with the prognosis and immune microenvironment of epithelial ovarian cancer (EOC). METHODS: We characte...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7591527/ https://www.ncbi.nlm.nih.gov/pubmed/32778818 http://dx.doi.org/10.1038/s41416-020-1026-0 |
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author | Yang, Moran Zhang, Guodong Wang, Yiying He, Mengdi Xu, Qing Lu, Jiaqi Liu, Haiou Xu, Congjian |
author_facet | Yang, Moran Zhang, Guodong Wang, Yiying He, Mengdi Xu, Qing Lu, Jiaqi Liu, Haiou Xu, Congjian |
author_sort | Yang, Moran |
collection | PubMed |
description | BACKGROUND: Tumour associated neutrophils (TANs) play a controversial role in regulating immune surveillance and immune evasion in various malignancies. Here, we investigated the relevance of TANs with the prognosis and immune microenvironment of epithelial ovarian cancer (EOC). METHODS: We characterised TANs using flow cytometric analysis and immunofluorescence analysis. The prognostic merit of TANs in EOC was evaluated using cox regression analysis. Furthermore, we explored the therapeutic merit of targeting Notch signalling in EOC and determined its involvement in the immune microenvironment. RESULTS: High level of TANs is associated with a dismal prognosis and immune tolerance in EOC. TANs impaired cytotoxic effects of CD8(+) T cells partly through Jagged2 (JAG2). Notch pathway blocked using γ-secretase inhibitor LY3039478 and anti-JAG2 antibody led to retarded tumour growth and augmented cytotoxic effects of CD8(+) T cells. IL-8 contributes to the recruitment of TANs and the induction of JAG2 expression in TANs. Blockade of CXCR2 signalling reduces tumour growth rate, accompanied by a decreasing amount of TANs and increasing activity of CD8(+) T cells. JAG2(+)TANs is an independent predictor of clinical outcomes. CONCLUSION: JAG2(+)TANs are closely linked to IL-8-driven immune evasion microenvironment and may serve as a promising therapeutic target for the reinvigoration of anti-tumour immunity. |
format | Online Article Text |
id | pubmed-7591527 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-75915272021-08-11 Tumour-associated neutrophils orchestrate intratumoural IL-8-driven immune evasion through Jagged2 activation in ovarian cancer Yang, Moran Zhang, Guodong Wang, Yiying He, Mengdi Xu, Qing Lu, Jiaqi Liu, Haiou Xu, Congjian Br J Cancer Article BACKGROUND: Tumour associated neutrophils (TANs) play a controversial role in regulating immune surveillance and immune evasion in various malignancies. Here, we investigated the relevance of TANs with the prognosis and immune microenvironment of epithelial ovarian cancer (EOC). METHODS: We characterised TANs using flow cytometric analysis and immunofluorescence analysis. The prognostic merit of TANs in EOC was evaluated using cox regression analysis. Furthermore, we explored the therapeutic merit of targeting Notch signalling in EOC and determined its involvement in the immune microenvironment. RESULTS: High level of TANs is associated with a dismal prognosis and immune tolerance in EOC. TANs impaired cytotoxic effects of CD8(+) T cells partly through Jagged2 (JAG2). Notch pathway blocked using γ-secretase inhibitor LY3039478 and anti-JAG2 antibody led to retarded tumour growth and augmented cytotoxic effects of CD8(+) T cells. IL-8 contributes to the recruitment of TANs and the induction of JAG2 expression in TANs. Blockade of CXCR2 signalling reduces tumour growth rate, accompanied by a decreasing amount of TANs and increasing activity of CD8(+) T cells. JAG2(+)TANs is an independent predictor of clinical outcomes. CONCLUSION: JAG2(+)TANs are closely linked to IL-8-driven immune evasion microenvironment and may serve as a promising therapeutic target for the reinvigoration of anti-tumour immunity. Nature Publishing Group UK 2020-08-11 2020-10-27 /pmc/articles/PMC7591527/ /pubmed/32778818 http://dx.doi.org/10.1038/s41416-020-1026-0 Text en © The Author(s), under exclusive licence to Cancer Research UK 2020 https://creativecommons.org/licenses/by/4.0/Note 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 Yang, Moran Zhang, Guodong Wang, Yiying He, Mengdi Xu, Qing Lu, Jiaqi Liu, Haiou Xu, Congjian Tumour-associated neutrophils orchestrate intratumoural IL-8-driven immune evasion through Jagged2 activation in ovarian cancer |
title | Tumour-associated neutrophils orchestrate intratumoural IL-8-driven immune evasion through Jagged2 activation in ovarian cancer |
title_full | Tumour-associated neutrophils orchestrate intratumoural IL-8-driven immune evasion through Jagged2 activation in ovarian cancer |
title_fullStr | Tumour-associated neutrophils orchestrate intratumoural IL-8-driven immune evasion through Jagged2 activation in ovarian cancer |
title_full_unstemmed | Tumour-associated neutrophils orchestrate intratumoural IL-8-driven immune evasion through Jagged2 activation in ovarian cancer |
title_short | Tumour-associated neutrophils orchestrate intratumoural IL-8-driven immune evasion through Jagged2 activation in ovarian cancer |
title_sort | tumour-associated neutrophils orchestrate intratumoural il-8-driven immune evasion through jagged2 activation in ovarian cancer |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7591527/ https://www.ncbi.nlm.nih.gov/pubmed/32778818 http://dx.doi.org/10.1038/s41416-020-1026-0 |
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