A Transcriptional Signature of IL-2 Expanded Natural Killer Cells Predicts More Favorable Prognosis in Bladder Cancer

Activation of natural killer (NK) cell function is regulated by cytokines, such as IL-2, and secreted factors upregulated in the tumor microenvironment, such as platelet-derived growth factor D (PDGF-DD). In order to elucidate a clinical role for these important regulators of NK cell function in ant...

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Autores principales:	Yuhan Sun, Alexander James Sedgwick, Md Abdullah-Al-Kamran Khan, Yaseelan Palarasah, Stefano Mangiola, Alexander David Barrow
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	NK cell bladder cancer prognosis NK receptors TCGA anti-tumor immunity Immunologic diseases. Allergy RC581-607
Acceso en línea:	https://doaj.org/article/9a25b716f78e484a8ead390e5f420cf3
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spelling	oai:doaj.org-article:9a25b716f78e484a8ead390e5f420cf32021-11-10T07:28:17ZA Transcriptional Signature of IL-2 Expanded Natural Killer Cells Predicts More Favorable Prognosis in Bladder Cancer1664-322410.3389/fimmu.2021.724107https://doaj.org/article/9a25b716f78e484a8ead390e5f420cf32021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fimmu.2021.724107/fullhttps://doaj.org/toc/1664-3224Activation of natural killer (NK) cell function is regulated by cytokines, such as IL-2, and secreted factors upregulated in the tumor microenvironment, such as platelet-derived growth factor D (PDGF-DD). In order to elucidate a clinical role for these important regulators of NK cell function in antitumor immunity, we generated transcriptional signatures representing resting, IL-2-expanded, and PDGF-DD-activated, NK cell phenotypes and established their abundance in The Cancer Genome Atlas bladder cancer (BLCA) dataset using CIBERSORT. The IL-2-expanded NK cell phenotype was the most abundant in low and high grades of BLCA tumors and was associated with improved prognosis. In contrast, PDGFD expression was associated with numerous cancer hallmark pathways in BLCA tumors compared with normal bladder tissue, and a high tumor abundance of PDGFD transcripts and the PDGF-DD-activated NK cell phenotype were associated with a poor BLCA prognosis. Finally, high tumor expression of transcripts encoding the activating NK cell receptors, KLRK1 and the CD160–TNFRSF14 receptor–ligand pair, was strongly correlated with the IL-2-expanded NK cell phenotype and improved BLCA prognosis. The transcriptional parameters we describe may be optimized to improve BLCA patient prognosis and risk stratification in the clinic and potentially provide gene targets of therapeutic significance for enhancing NK cell antitumor immunity in BLCA.Yuhan SunAlexander James SedgwickMd Abdullah-Al-Kamran KhanYaseelan PalarasahStefano MangiolaAlexander David BarrowFrontiers Media S.A.articleNK cellbladder cancerprognosisNK receptorsTCGAanti-tumor immunityImmunologic diseases. AllergyRC581-607ENFrontiers in Immunology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	NK cell bladder cancer prognosis NK receptors TCGA anti-tumor immunity Immunologic diseases. Allergy RC581-607
spellingShingle	NK cell bladder cancer prognosis NK receptors TCGA anti-tumor immunity Immunologic diseases. Allergy RC581-607 Yuhan Sun Alexander James Sedgwick Md Abdullah-Al-Kamran Khan Yaseelan Palarasah Stefano Mangiola Alexander David Barrow A Transcriptional Signature of IL-2 Expanded Natural Killer Cells Predicts More Favorable Prognosis in Bladder Cancer
description	Activation of natural killer (NK) cell function is regulated by cytokines, such as IL-2, and secreted factors upregulated in the tumor microenvironment, such as platelet-derived growth factor D (PDGF-DD). In order to elucidate a clinical role for these important regulators of NK cell function in antitumor immunity, we generated transcriptional signatures representing resting, IL-2-expanded, and PDGF-DD-activated, NK cell phenotypes and established their abundance in The Cancer Genome Atlas bladder cancer (BLCA) dataset using CIBERSORT. The IL-2-expanded NK cell phenotype was the most abundant in low and high grades of BLCA tumors and was associated with improved prognosis. In contrast, PDGFD expression was associated with numerous cancer hallmark pathways in BLCA tumors compared with normal bladder tissue, and a high tumor abundance of PDGFD transcripts and the PDGF-DD-activated NK cell phenotype were associated with a poor BLCA prognosis. Finally, high tumor expression of transcripts encoding the activating NK cell receptors, KLRK1 and the CD160–TNFRSF14 receptor–ligand pair, was strongly correlated with the IL-2-expanded NK cell phenotype and improved BLCA prognosis. The transcriptional parameters we describe may be optimized to improve BLCA patient prognosis and risk stratification in the clinic and potentially provide gene targets of therapeutic significance for enhancing NK cell antitumor immunity in BLCA.
format	article
author	Yuhan Sun Alexander James Sedgwick Md Abdullah-Al-Kamran Khan Yaseelan Palarasah Stefano Mangiola Alexander David Barrow
author_facet	Yuhan Sun Alexander James Sedgwick Md Abdullah-Al-Kamran Khan Yaseelan Palarasah Stefano Mangiola Alexander David Barrow
author_sort	Yuhan Sun
title	A Transcriptional Signature of IL-2 Expanded Natural Killer Cells Predicts More Favorable Prognosis in Bladder Cancer
title_short	A Transcriptional Signature of IL-2 Expanded Natural Killer Cells Predicts More Favorable Prognosis in Bladder Cancer
title_full	A Transcriptional Signature of IL-2 Expanded Natural Killer Cells Predicts More Favorable Prognosis in Bladder Cancer
title_fullStr	A Transcriptional Signature of IL-2 Expanded Natural Killer Cells Predicts More Favorable Prognosis in Bladder Cancer
title_full_unstemmed	A Transcriptional Signature of IL-2 Expanded Natural Killer Cells Predicts More Favorable Prognosis in Bladder Cancer
title_sort	transcriptional signature of il-2 expanded natural killer cells predicts more favorable prognosis in bladder cancer
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/9a25b716f78e484a8ead390e5f420cf3
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A Transcriptional Signature of IL-2 Expanded Natural Killer Cells Predicts More Favorable Prognosis in Bladder Cancer

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