Diagnostic and prognostic implications of caspase‐1 and pd‐l1 co‐expression patterns in myelodysplastic syndromes

Abstract

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 higherrisk 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 noninflammatory (Casp1low/PD‐L1low) and inflammatory conditions (Casp1high/PD‐L1high). Further validation is warranted in larger, prospective studies.