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: | , , , , , , , , , |
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| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
MDPI AG
2021
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| Materias: | |
| Acceso en línea: | https://doaj.org/article/bf4a47d021b6457da642e660955cba02 |
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| Sumario: | 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. |
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