FOXP3+ T cells in uterine sarcomas are associated with favorable prognosis, low extracellular matrix expression and reduced YAP activation

Abstract Uterine sarcomas are rare but deadly malignancies without effective treatment. Immunotherapy is a promising new approach to treat these tumors but has shown heterogeneous effects in sarcoma patients. With the goal of identifying key factors for improved patient treatment, we characterized t...

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Autores principales:	Okan Gultekin, Jordi Gonzalez-Molina, Elin Hardell, Lidia Moyano-Galceran, Nicholas Mitsios, Jan Mulder, Georgia Kokaraki, Anders Isaksson, Dhifaf Sarhan, Kaisa Lehti, Joseph W. Carlson
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/eda4826495d543a98d261183c1886ac9
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spelling	oai:doaj.org-article:eda4826495d543a98d261183c1886ac92021-11-21T12:09:18ZFOXP3+ T cells in uterine sarcomas are associated with favorable prognosis, low extracellular matrix expression and reduced YAP activation10.1038/s41698-021-00236-62397-768Xhttps://doaj.org/article/eda4826495d543a98d261183c1886ac92021-11-01T00:00:00Zhttps://doi.org/10.1038/s41698-021-00236-6https://doaj.org/toc/2397-768XAbstract Uterine sarcomas are rare but deadly malignancies without effective treatment. Immunotherapy is a promising new approach to treat these tumors but has shown heterogeneous effects in sarcoma patients. With the goal of identifying key factors for improved patient treatment, we characterized the tumor immune landscape in 58 uterine sarcoma cases with full clinicopathological annotation. Immune cell characterization revealed the overall prevalence of FOXP3+ cells and pro-tumor M2-like macrophages. Hierarchical clustering of patients showed four tumor type-independent immune signatures, where infiltration of FOXP3+ cells and M1-like macrophages associated with favorable prognosis. High CD8+/FOXP3+ ratio in UUS and ESS correlated with poor survival, upregulation of immunosuppressive markers, extracellular matrix (ECM)-related genes and proteins, and YAP activation. This study shows that uterine sarcomas present distinct immune signatures with prognostic value, independent of tumor type, and suggests that targeting the ECM could be beneficial for future treatments.Okan GultekinJordi Gonzalez-MolinaElin HardellLidia Moyano-GalceranNicholas MitsiosJan MulderGeorgia KokarakiAnders IsakssonDhifaf SarhanKaisa LehtiJoseph W. CarlsonNature PortfolioarticleNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENnpj Precision Oncology, Vol 5, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Okan Gultekin Jordi Gonzalez-Molina Elin Hardell Lidia Moyano-Galceran Nicholas Mitsios Jan Mulder Georgia Kokaraki Anders Isaksson Dhifaf Sarhan Kaisa Lehti Joseph W. Carlson FOXP3+ T cells in uterine sarcomas are associated with favorable prognosis, low extracellular matrix expression and reduced YAP activation
description	Abstract Uterine sarcomas are rare but deadly malignancies without effective treatment. Immunotherapy is a promising new approach to treat these tumors but has shown heterogeneous effects in sarcoma patients. With the goal of identifying key factors for improved patient treatment, we characterized the tumor immune landscape in 58 uterine sarcoma cases with full clinicopathological annotation. Immune cell characterization revealed the overall prevalence of FOXP3+ cells and pro-tumor M2-like macrophages. Hierarchical clustering of patients showed four tumor type-independent immune signatures, where infiltration of FOXP3+ cells and M1-like macrophages associated with favorable prognosis. High CD8+/FOXP3+ ratio in UUS and ESS correlated with poor survival, upregulation of immunosuppressive markers, extracellular matrix (ECM)-related genes and proteins, and YAP activation. This study shows that uterine sarcomas present distinct immune signatures with prognostic value, independent of tumor type, and suggests that targeting the ECM could be beneficial for future treatments.
format	article
author	Okan Gultekin Jordi Gonzalez-Molina Elin Hardell Lidia Moyano-Galceran Nicholas Mitsios Jan Mulder Georgia Kokaraki Anders Isaksson Dhifaf Sarhan Kaisa Lehti Joseph W. Carlson
author_facet	Okan Gultekin Jordi Gonzalez-Molina Elin Hardell Lidia Moyano-Galceran Nicholas Mitsios Jan Mulder Georgia Kokaraki Anders Isaksson Dhifaf Sarhan Kaisa Lehti Joseph W. Carlson
author_sort	Okan Gultekin
title	FOXP3+ T cells in uterine sarcomas are associated with favorable prognosis, low extracellular matrix expression and reduced YAP activation
title_short	FOXP3+ T cells in uterine sarcomas are associated with favorable prognosis, low extracellular matrix expression and reduced YAP activation
title_full	FOXP3+ T cells in uterine sarcomas are associated with favorable prognosis, low extracellular matrix expression and reduced YAP activation
title_fullStr	FOXP3+ T cells in uterine sarcomas are associated with favorable prognosis, low extracellular matrix expression and reduced YAP activation
title_full_unstemmed	FOXP3+ T cells in uterine sarcomas are associated with favorable prognosis, low extracellular matrix expression and reduced YAP activation
title_sort	foxp3+ t cells in uterine sarcomas are associated with favorable prognosis, low extracellular matrix expression and reduced yap activation
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/eda4826495d543a98d261183c1886ac9
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FOXP3+ T cells in uterine sarcomas are associated with favorable prognosis, low extracellular matrix expression and reduced YAP activation

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