Dataset Information

Tumor microenvironment-derived S100A8/A9 is a novel prognostic biomarker for advanced melanoma patients and during immunotherapy with anti-PD-1 antibodies.

ABSTRACT: BACKGROUND:Predicting metastasis in melanoma patients is important for disease management and could help to identify those who might benefit from adjuvant treatment. The aim of this study was to investigate whether the tumor microenvironment-derived protein S100A8/A9 qualifies as prognostic marker for melanoma patients, also in the setting of immunotherapy. METHODS:S100A8/A9 gene and protein expression were analyzed on melanocytic nevi, primary melanomas and metastases using a cDNA library and three independent tissue-microarrays (TMA). Serum levels of S100A8/A9 were measured using a specific ELISA in two independent cohorts of 354 stage III and stage IV melanoma patients as well as in two independent cohorts of patients treated with the PD-1 antibody pembrolizumab. RESULTS:cDNA analysis revealed an upregulation of S100A8 and S100A9 gene expression in melanoma metastases compared to primary melanomas. Significantly higher numbers of infiltrating S100A8/A9 positive cells were found in tissue samples of metastasizing primary melanomas compared to non-metastasizing melanomas (P??5.5?mg/l were associated with impaired overall survival in two independent cohorts (both P?

SUBMITTER: Wagner NB

PROVIDER: S-EPMC6896585 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Tumor microenvironment-derived S100A8/A9 is a novel prognostic biomarker for advanced melanoma patients and during immunotherapy with anti-PD-1 antibodies.

Wagner Nikolaus B NB Weide Benjamin B Gries Mirko M Reith Maike M Tarnanidis Kathrin K Schuermans Valerie V Kemper Charlotte C Kehrel Coretta C Funder Anne A Lichtenberger Ramtin R Sucker Antje A Herpel Esther E Holland-Letz Tim T Schadendorf Dirk D Garbe Claus C Umansky Viktor V Utikal Jochen J Gebhardt Christoffer C

Journal for immunotherapy of cancer 20191205 1

<h4>Background</h4>Predicting metastasis in melanoma patients is important for disease management and could help to identify those who might benefit from adjuvant treatment. The aim of this study was to investigate whether the tumor microenvironment-derived protein S100A8/A9 qualifies as prognostic marker for melanoma patients, also in the setting of immunotherapy.<h4>Methods</h4>S100A8/A9 gene and protein expression were analyzed on melanocytic nevi, primary melanomas and metastases using a cDN ...[more]

PMID: 31806053

Similar Datasets

Project description:BackgroundMyocardial infarction (MI) triggers myelopoiesis, resulting in heightened production of neutrophils. However, the mechanisms that sustain their production and recruitment to the injured heart are unclear.MethodsUsing a mouse model of the permanent ligation of the left anterior descending artery and flow cytometry, we first characterized the temporal and spatial effects of MI on different myeloid cell types. We next performed global transcriptome analysis of different cardiac cell types within the infarct to identify the drivers of the acute inflammatory response and the underlying signaling pathways. Using a combination of genetic and pharmacological strategies, we identified the sequelae of events that led to MI-induced myelopoiesis. Cardiac function was assessed by echocardiography. The association of early indexes of neutrophilia with major adverse cardiovascular events was studied in a cohort of patients with acute MI.ResultsInduction of MI results in rapid recruitment of neutrophils to the infarct, where they release specific alarmins, S100A8 and S100A9. These alarmins bind to the Toll-like receptor 4 and prime the nod-like receptor family pyrin domain-containing 3 inflammasome in naïve neutrophils and promote interleukin-1β secretion. The released interleukin-1β interacts with its receptor (interleukin 1 receptor type 1) on hematopoietic stem and progenitor cells in the bone marrow and stimulates granulopoiesis in a cell-autonomous manner. Genetic or pharmacological strategies aimed at disruption of S100A8/A9 and their downstream signaling cascade suppress MI-induced granulopoiesis and improve cardiac function. Furthermore, in patients with acute coronary syndrome, higher neutrophil count on admission and after revascularization correlates positively with major adverse cardiovascular disease outcomes.ConclusionsOur study provides novel evidence for the primary role of neutrophil-derived alarmins (S100A8/A9) in dictating the nature of the ensuing inflammatory response after myocardial injury. Therapeutic strategies aimed at disruption of S100A8/A9 signaling or their downstream mediators (eg, nod-like receptor family pyrin domain-containing 3 inflammasome, interleukin-1β) in neutrophils suppress granulopoiesis and may improve cardiac function in patients with acute coronary syndrome.

Dataset Information

Tumor microenvironment-derived S100A8/A9 is a novel prognostic biomarker for advanced melanoma patients and during immunotherapy with anti-PD-1 antibodies.

Publications

Tumor microenvironment-derived S100A8/A9 is a novel prognostic biomarker for advanced melanoma patients and during immunotherapy with anti-PD-1 antibodies.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets