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

Abstract

Simple SummaryMyelodysplastic syndromes (MDS) originate from mutated hematopoietic stem and progenitor cells. Despite recent advances in genetics, the mechanisms involved in clonal progression remain largely unknown. We performed an exploratory, case-control study to identify immune-related biomarkers with diagnostic and prognostic utility. Our study suggests a combined Casp1/PD-L1 assessment to distinguish reactive conditions from lower- and higher-risk MDS. These immune-related biomarkers may help to personalize immuno-therapies but require further validation in prospective studies.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 (n = 3) and inflammatory conditions (n = 6). Patients were stratified in groups of lower (n = 10) and higher risk (n = 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 (p = 0.003). We found a discordant co-expression of Casp1/PD-L1 in MDS (rho = −0.41, p = 0.07) compared with a concordant co-expression in controls (rho = 0.64, p = 0.06). Neutrophil counts correlated directly with Casp1 (rho = 0.57, p = 0.009) but inversely with PD-L1 expression (rho = −0.58, p = 0.007). Conclusion: We identified characteristic discordant co-expression patterns in lower- (Casp1high/PD-L1low) and higher-risk MDS (Casp1low/PD-L1high), contrasting with concordant patterns in the non-inflammatory (Casp1low/PD-L1low) and inflammatory conditions (Casp1high/PD-L1high). Further validation is warranted in larger, prospective studies.