Please use this identifier to cite or link to this item: http://ahro.austin.org.au/austinjspui/handle/1/20881
Title: A Gene Signature Predicting Natural Killer Cell Infiltration and Improved Survival in Melanoma Patients.
Authors: Cursons, Joseph;Souza-Fonseca-Guimaraes, Fernando;Foroutan, Momeneh;Anderson, Ashley;Hollande, Frédéric;Hediyeh-Zadeh, Soroor;Behren, Andreas;Huntington, Nicholas D;Davis, Melissa J
Affiliation: Bioinformatics Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia
Department of Biochemistry, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Parkville, Victoria, Australia
Biomedicine Discovery Institute and the Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria, Australia
Olivia Newton-John Cancer Research Institute, Heidelberg, Victoria, Australia
School of Cancer Medicine, La Trobe University, Melbourne, Victoria, Australia
Department of Clinical Pathology, The University of Melbourne Centre for Cancer Research, Victorian Comprehensive Cancer Centre, Melbourne, Victoria, Australia
Division of Molecular Immunology, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia
Department of Medical Biology, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Parkville, Victoria, Australia
Issue Date: 14-May-2019
EDate: 2019-05-14
Citation: Cancer immunology research 2019; online first: 14 May
Abstract: Natural killer (NK) cell activity is essential for initiating antitumor responses and may be linked to immunotherapy success. NK cells and other innate immune components could be exploitable for cancer treatment, which drives the need for tools and methods that identify therapeutic avenues. Here, we extend our gene-set scoring method singscore to investigate NK cell infiltration by applying RNA-seq analysis to samples from bulk tumors. Computational methods have been developed for the deconvolution of immune cell types within solid tumors. We have taken the NK cell gene signatures from several such tools, then curated the gene list using a comparative analysis of tumors and immune cell types. Using a gene-set scoring method to investigate RNA-seq data from The Cancer Genome Atlas (TCGA), we show that patients with metastatic cutaneous melanoma have an improved survival rate if their tumor shows evidence of NK cell infiltration. Furthermore, these survival effects are enhanced in tumors that show higher expression of genes that encode NK cell stimuli such as the cytokine IL15 Using this signature, we then examine transcriptomic data to identify tumor and stromal components that may influence the penetrance of NK cells into solid tumors. Our results provide evidence that NK cells play a role in the regulation of human tumors and highlight potential survival effects associated with increased NK cell activity. Our computational analysis identifies putative gene targets that may be of therapeutic value for boosting NK cell antitumor immunity.
URI: http://ahro.austin.org.au/austinjspui/handle/1/20881
DOI: 10.1158/2326-6066.CIR-18-0500
ORCID: 0000-0002-5053-4540
0000-0002-1440-0457
0000-0002-6981-346X
0000-0001-7513-6779
0000-0001-5329-280X
0000-0002-5267-7211
PubMed URL: 31088844
Type: Journal Article
Appears in Collections:Journal articles

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