Overexpression of S100A9 in tumor stroma contribute to immune evasion of NK/T cell lymphoma and predict poor response rate

Abstract NK/T cell lymphoma (NKTCL) represents an aggressive lymphoid malignancy characterized by dismal prognosis. Immune-checkpoint blockade has shown promising efficacy in NKTCL. However, the molecular mechanisms underlying immune evasion in NKTCL have never been explored. Here, proteomic analysi...

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Autores principales:	Zhiyuan Zhou, Xinfeng Chen, Zhaoming Li, Xinhua Wang, Mingzhi Zhang
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/05525cb9d09a4e07bc1bc70db11f00f0
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spelling	oai:doaj.org-article:05525cb9d09a4e07bc1bc70db11f00f02021-12-02T14:49:11ZOverexpression of S100A9 in tumor stroma contribute to immune evasion of NK/T cell lymphoma and predict poor response rate10.1038/s41598-021-90794-32045-2322https://doaj.org/article/05525cb9d09a4e07bc1bc70db11f00f02021-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-90794-3https://doaj.org/toc/2045-2322Abstract NK/T cell lymphoma (NKTCL) represents an aggressive lymphoid malignancy characterized by dismal prognosis. Immune-checkpoint blockade has shown promising efficacy in NKTCL. However, the molecular mechanisms underlying immune evasion in NKTCL have never been explored. Here, proteomic analysis was used to identify the differentially expressed proteins between NKTCL patients and healthy individuals. We found that S100A9, an immunosuppressive molecule, was much higher in NKTCL patients both in serum and tumor stroma. Elevated level of S100A9 was associated with advanced stage, poor overall response and early recurrence. Moreover, percentage of myeloid-derived suppressor cells (MDSCs) in peripheral blood was positively correlated with levels of S100A9. Low concentration of S100A9 promoted proliferation of NKTCL cells, while did not affect cell apoptosis and cell cycles. Furthermore, programmed death ligand 1 (PD-L1) expression on NKTCL cells was up-regulated by S100A9 through activation of ERK1/2 signaling. Inhibition of ERK1/2 signaling significantly decreased tumor growth and PD-L1 expression induced by S100A9. In conclusion, our research firstly identified S100A9 as an immune suppressor in the tumorigenesis of NKTCL via accumulation of MDSCs and upregulation of PD-L1 expression. S100A9 may serve as a potential target to increase the efficacy of immunotherapy in NKTCL.Zhiyuan ZhouXinfeng ChenZhaoming LiXinhua WangMingzhi ZhangNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Zhiyuan Zhou Xinfeng Chen Zhaoming Li Xinhua Wang Mingzhi Zhang Overexpression of S100A9 in tumor stroma contribute to immune evasion of NK/T cell lymphoma and predict poor response rate
description	Abstract NK/T cell lymphoma (NKTCL) represents an aggressive lymphoid malignancy characterized by dismal prognosis. Immune-checkpoint blockade has shown promising efficacy in NKTCL. However, the molecular mechanisms underlying immune evasion in NKTCL have never been explored. Here, proteomic analysis was used to identify the differentially expressed proteins between NKTCL patients and healthy individuals. We found that S100A9, an immunosuppressive molecule, was much higher in NKTCL patients both in serum and tumor stroma. Elevated level of S100A9 was associated with advanced stage, poor overall response and early recurrence. Moreover, percentage of myeloid-derived suppressor cells (MDSCs) in peripheral blood was positively correlated with levels of S100A9. Low concentration of S100A9 promoted proliferation of NKTCL cells, while did not affect cell apoptosis and cell cycles. Furthermore, programmed death ligand 1 (PD-L1) expression on NKTCL cells was up-regulated by S100A9 through activation of ERK1/2 signaling. Inhibition of ERK1/2 signaling significantly decreased tumor growth and PD-L1 expression induced by S100A9. In conclusion, our research firstly identified S100A9 as an immune suppressor in the tumorigenesis of NKTCL via accumulation of MDSCs and upregulation of PD-L1 expression. S100A9 may serve as a potential target to increase the efficacy of immunotherapy in NKTCL.
format	article
author	Zhiyuan Zhou Xinfeng Chen Zhaoming Li Xinhua Wang Mingzhi Zhang
author_facet	Zhiyuan Zhou Xinfeng Chen Zhaoming Li Xinhua Wang Mingzhi Zhang
author_sort	Zhiyuan Zhou
title	Overexpression of S100A9 in tumor stroma contribute to immune evasion of NK/T cell lymphoma and predict poor response rate
title_short	Overexpression of S100A9 in tumor stroma contribute to immune evasion of NK/T cell lymphoma and predict poor response rate
title_full	Overexpression of S100A9 in tumor stroma contribute to immune evasion of NK/T cell lymphoma and predict poor response rate
title_fullStr	Overexpression of S100A9 in tumor stroma contribute to immune evasion of NK/T cell lymphoma and predict poor response rate
title_full_unstemmed	Overexpression of S100A9 in tumor stroma contribute to immune evasion of NK/T cell lymphoma and predict poor response rate
title_sort	overexpression of s100a9 in tumor stroma contribute to immune evasion of nk/t cell lymphoma and predict poor response rate
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/05525cb9d09a4e07bc1bc70db11f00f0
work_keys_str_mv	AT zhiyuanzhou overexpressionofs100a9intumorstromacontributetoimmuneevasionofnktcelllymphomaandpredictpoorresponserate AT xinfengchen overexpressionofs100a9intumorstromacontributetoimmuneevasionofnktcelllymphomaandpredictpoorresponserate AT zhaomingli overexpressionofs100a9intumorstromacontributetoimmuneevasionofnktcelllymphomaandpredictpoorresponserate AT xinhuawang overexpressionofs100a9intumorstromacontributetoimmuneevasionofnktcelllymphomaandpredictpoorresponserate AT mingzhizhang overexpressionofs100a9intumorstromacontributetoimmuneevasionofnktcelllymphomaandpredictpoorresponserate
_version_	1718389489913561088

Overexpression of S100A9 in tumor stroma contribute to immune evasion of NK/T cell lymphoma and predict poor response rate

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