SIRT2 promotes murine melanoma progression through natural killer cell inhibition

Abstract SIRT2, an NAD+-dependent histone deacetylase, has been shown to play a pivotal role in various physiological processes, however, its role in cancer is currently controversial. In recent years, SIRT2 has been described as both a tumor suppressor and oncogene with divergent expression and fun...

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Autores principales:	Manchao Zhang, Scarlett Acklin, John Gillenwater, Wuying Du, Mousumi Patra, Hao Yu, Bo Xu, Jianhua Yu, Fen Xia
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/e610561f6fb24f419028b523a030e68e
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spelling	oai:doaj.org-article:e610561f6fb24f419028b523a030e68e2021-12-02T17:12:21ZSIRT2 promotes murine melanoma progression through natural killer cell inhibition10.1038/s41598-021-92445-z2045-2322https://doaj.org/article/e610561f6fb24f419028b523a030e68e2021-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-92445-zhttps://doaj.org/toc/2045-2322Abstract SIRT2, an NAD+-dependent histone deacetylase, has been shown to play a pivotal role in various physiological processes, however, its role in cancer is currently controversial. In recent years, SIRT2 has been described as both a tumor suppressor and oncogene with divergent expression and function in various malignancies. Using murine allograft melanoma models, our results suggest increased systemic expression of SIRT2 promotes tumor progression. In this study, SIRT2-overexpressing mice exhibited enhanced tumor growth and larger tumor volumes compared to their wild-type littermates. Mechanistically, systemic overexpression of SIRT2 reduces the number of tumor-infiltrating natural killer (NK) cells and suppresses NK cell function and proliferation within the tumor microenvironment (TME). Furthermore, despite the enhancing effect of NK cell depletion on tumor volume and growth rate in wild-type littermate mice, this effect was diminished in SIRT2-overexpressing mice. Lastly, pharmacological inhibition of SIRT2 increases NK cell tumor infiltration and suppresses allograft melanoma tumor growth. The findings of this study identify a dynamic functional interaction between systemic SIRT2 and NK cell activity, which controls melanoma tumor progression. Given the recent renewed interest in NK-cell-mediated immunotherapy response, SIRT2 could present a new opportunity to mediate immunotherapy response and resistance.Manchao ZhangScarlett AcklinJohn GillenwaterWuying DuMousumi PatraHao YuBo XuJianhua YuFen XiaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Manchao Zhang Scarlett Acklin John Gillenwater Wuying Du Mousumi Patra Hao Yu Bo Xu Jianhua Yu Fen Xia SIRT2 promotes murine melanoma progression through natural killer cell inhibition
description	Abstract SIRT2, an NAD+-dependent histone deacetylase, has been shown to play a pivotal role in various physiological processes, however, its role in cancer is currently controversial. In recent years, SIRT2 has been described as both a tumor suppressor and oncogene with divergent expression and function in various malignancies. Using murine allograft melanoma models, our results suggest increased systemic expression of SIRT2 promotes tumor progression. In this study, SIRT2-overexpressing mice exhibited enhanced tumor growth and larger tumor volumes compared to their wild-type littermates. Mechanistically, systemic overexpression of SIRT2 reduces the number of tumor-infiltrating natural killer (NK) cells and suppresses NK cell function and proliferation within the tumor microenvironment (TME). Furthermore, despite the enhancing effect of NK cell depletion on tumor volume and growth rate in wild-type littermate mice, this effect was diminished in SIRT2-overexpressing mice. Lastly, pharmacological inhibition of SIRT2 increases NK cell tumor infiltration and suppresses allograft melanoma tumor growth. The findings of this study identify a dynamic functional interaction between systemic SIRT2 and NK cell activity, which controls melanoma tumor progression. Given the recent renewed interest in NK-cell-mediated immunotherapy response, SIRT2 could present a new opportunity to mediate immunotherapy response and resistance.
format	article
author	Manchao Zhang Scarlett Acklin John Gillenwater Wuying Du Mousumi Patra Hao Yu Bo Xu Jianhua Yu Fen Xia
author_facet	Manchao Zhang Scarlett Acklin John Gillenwater Wuying Du Mousumi Patra Hao Yu Bo Xu Jianhua Yu Fen Xia
author_sort	Manchao Zhang
title	SIRT2 promotes murine melanoma progression through natural killer cell inhibition
title_short	SIRT2 promotes murine melanoma progression through natural killer cell inhibition
title_full	SIRT2 promotes murine melanoma progression through natural killer cell inhibition
title_fullStr	SIRT2 promotes murine melanoma progression through natural killer cell inhibition
title_full_unstemmed	SIRT2 promotes murine melanoma progression through natural killer cell inhibition
title_sort	sirt2 promotes murine melanoma progression through natural killer cell inhibition
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/e610561f6fb24f419028b523a030e68e
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SIRT2 promotes murine melanoma progression through natural killer cell inhibition

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