Diagnostic and Prognostic Implications of Caspase-1 and PD-L1 Co-Expression Patterns in Myelodysplastic Syndromes

Background: The inflammasome plays an essential role in lower risk MDS and immune subversion, with the up-regulation of immune checkpoint molecules in the progression to higher-risk disease. In this study, we explored the utility of immune-related biomarkers for the diagnosis and prognosis of MDS. M...

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Autores principales:	Johannes R. Graf, Stefan Forster, Frido K. Bruehl, Yara Banz, Mahmoud Hallal, Justine Brodard, Vera Ulrike Bacher, Ramanjaneyulu Allam, Christian M. Schürch, Nicolas Bonadies
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	myelodysplastic syndromes inflammasome immune check-point immune-related biomarkers diagnosis prognosis Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/bf4a47d021b6457da642e660955cba02
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spelling	oai:doaj.org-article:bf4a47d021b6457da642e660955cba022021-11-25T17:03:00ZDiagnostic and Prognostic Implications of Caspase-1 and PD-L1 Co-Expression Patterns in Myelodysplastic Syndromes10.3390/cancers132257122072-6694https://doaj.org/article/bf4a47d021b6457da642e660955cba022021-11-01T00:00:00Zhttps://www.mdpi.com/2072-6694/13/22/5712https://doaj.org/toc/2072-6694Background: The inflammasome plays an essential role in lower risk MDS and immune subversion, with the up-regulation of immune checkpoint molecules in the progression to higher-risk disease. In this study, we explored the utility of immune-related biomarkers for the diagnosis and prognosis of MDS. Methods: We performed an exploratory, case-control study with 20 randomly selected MDS patients and nine controls with non-inflammatory (<i>n</i> = 3) and inflammatory conditions (<i>n</i> = 6). Patients were stratified in groups of lower (<i>n</i> = 10) and higher risk (<i>n</i> = 10) using IPSS-R. For the exploration of inflammasome and immune checkpoint activities, the expression of caspase-1 (Casp1), programmed cell death protein 1 (PD-1) and its ligand (PD-L1) were assessed in bone marrow samples using immunohistochemistry. Results: In multivariate analysis, we observed significant differences for Casp1 but not PD1/PD-L1 expression in our four conditions (<i>p</i> = 0.003). We found a discordant co-expression of Casp1/PD-L1 in MDS (rho = −0.41, <i>p</i> = 0.07) compared with a concordant co-expression in controls (rho = 0.64, <i>p</i> = 0.06). Neutrophil counts correlated directly with Casp1 (rho = 0.57, <i>p =</i> 0.009) but inversely with PD-L1 expression (rho = −0.58, <i>p</i> = 0.007). Conclusion: We identified characteristic discordant co-expression patterns in lower- (Casp1<sub>high</sub>/PD-L1<sub>low</sub>) and higher-risk MDS (Casp1<sub>low</sub>/PD-L1<sub>high</sub>), contrasting with concordant patterns in the non-inflammatory (Casp1<sub>low</sub>/PD-L1<sub>low</sub>) and inflammatory conditions (Casp1<sub>high</sub>/PD-L1<sub>high</sub>). Further validation is warranted in larger, prospective studies.Johannes R. GrafStefan ForsterFrido K. BruehlYara BanzMahmoud HallalJustine BrodardVera Ulrike BacherRamanjaneyulu AllamChristian M. SchürchNicolas BonadiesMDPI AGarticlemyelodysplastic syndromesinflammasomeimmune check-pointimmune-related biomarkersdiagnosisprognosisNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENCancers, Vol 13, Iss 5712, p 5712 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	myelodysplastic syndromes inflammasome immune check-point immune-related biomarkers diagnosis prognosis Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	myelodysplastic syndromes inflammasome immune check-point immune-related biomarkers diagnosis prognosis Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Johannes R. Graf Stefan Forster Frido K. Bruehl Yara Banz Mahmoud Hallal Justine Brodard Vera Ulrike Bacher Ramanjaneyulu Allam Christian M. Schürch Nicolas Bonadies Diagnostic and Prognostic Implications of Caspase-1 and PD-L1 Co-Expression Patterns in Myelodysplastic Syndromes
description	Background: The inflammasome plays an essential role in lower risk MDS and immune subversion, with the up-regulation of immune checkpoint molecules in the progression to higher-risk disease. In this study, we explored the utility of immune-related biomarkers for the diagnosis and prognosis of MDS. Methods: We performed an exploratory, case-control study with 20 randomly selected MDS patients and nine controls with non-inflammatory (<i>n</i> = 3) and inflammatory conditions (<i>n</i> = 6). Patients were stratified in groups of lower (<i>n</i> = 10) and higher risk (<i>n</i> = 10) using IPSS-R. For the exploration of inflammasome and immune checkpoint activities, the expression of caspase-1 (Casp1), programmed cell death protein 1 (PD-1) and its ligand (PD-L1) were assessed in bone marrow samples using immunohistochemistry. Results: In multivariate analysis, we observed significant differences for Casp1 but not PD1/PD-L1 expression in our four conditions (<i>p</i> = 0.003). We found a discordant co-expression of Casp1/PD-L1 in MDS (rho = −0.41, <i>p</i> = 0.07) compared with a concordant co-expression in controls (rho = 0.64, <i>p</i> = 0.06). Neutrophil counts correlated directly with Casp1 (rho = 0.57, <i>p =</i> 0.009) but inversely with PD-L1 expression (rho = −0.58, <i>p</i> = 0.007). Conclusion: We identified characteristic discordant co-expression patterns in lower- (Casp1<sub>high</sub>/PD-L1<sub>low</sub>) and higher-risk MDS (Casp1<sub>low</sub>/PD-L1<sub>high</sub>), contrasting with concordant patterns in the non-inflammatory (Casp1<sub>low</sub>/PD-L1<sub>low</sub>) and inflammatory conditions (Casp1<sub>high</sub>/PD-L1<sub>high</sub>). Further validation is warranted in larger, prospective studies.
format	article
author	Johannes R. Graf Stefan Forster Frido K. Bruehl Yara Banz Mahmoud Hallal Justine Brodard Vera Ulrike Bacher Ramanjaneyulu Allam Christian M. Schürch Nicolas Bonadies
author_facet	Johannes R. Graf Stefan Forster Frido K. Bruehl Yara Banz Mahmoud Hallal Justine Brodard Vera Ulrike Bacher Ramanjaneyulu Allam Christian M. Schürch Nicolas Bonadies
author_sort	Johannes R. Graf
title	Diagnostic and Prognostic Implications of Caspase-1 and PD-L1 Co-Expression Patterns in Myelodysplastic Syndromes
title_short	Diagnostic and Prognostic Implications of Caspase-1 and PD-L1 Co-Expression Patterns in Myelodysplastic Syndromes
title_full	Diagnostic and Prognostic Implications of Caspase-1 and PD-L1 Co-Expression Patterns in Myelodysplastic Syndromes
title_fullStr	Diagnostic and Prognostic Implications of Caspase-1 and PD-L1 Co-Expression Patterns in Myelodysplastic Syndromes
title_full_unstemmed	Diagnostic and Prognostic Implications of Caspase-1 and PD-L1 Co-Expression Patterns in Myelodysplastic Syndromes
title_sort	diagnostic and prognostic implications of caspase-1 and pd-l1 co-expression patterns in myelodysplastic syndromes
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/bf4a47d021b6457da642e660955cba02
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Diagnostic and Prognostic Implications of Caspase-1 and PD-L1 Co-Expression Patterns in Myelodysplastic Syndromes

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