INCREASED PROGRAMMED DEATH LIGAND-1 EXPRESSION LEADS TO WORSE CLINICAL FEATURES IN PATIENTS WITH MYELODYSPLASTIC SYNDROME

Abstract

Immune checkpoints are regulators of the immune system response that allow self-tolerance. Molecules such as Programmed Cell Death Protein 1 (PD-1) and its Ligand (PD-L1) participate in the immune checkpoint by signaling co-inhibition of lymphocyte responses. In cancers, PD-L1 expression is associated with the immune evasion mechanism, which favors tumor growth. The role of PD-L1 is already known for several solid tumors and anti-PD-L1 drugs are used for treatment. Myelodysplastic Syndrome (MDS) is a heterogeneous bone marrow disease with an increased risk of progression to Acute Myeloid Leukemia (AML). The pathogenesis of MDS involves several factors, including alterations in immune pathways. However, the role of PD-L1 still lacks understanding in this disease. The aim of this study was to evaluate if PD-L1 gene expression would be linked to clinical and prognostic features in patients with myelodysplastic syndrome. In this study, we evaluated PD-L1 mRNA expression by real-time PCR using TaqMan ® probes. Fifty-three patients classified according to WHO 2016 were analyzed. We observed that patients with dyserythropoiesis have higher PD-L1 expression than patients without dyserythropoiesis (p = 0.050). Furthermore, patients classified as excess of blasts 2 (MDS-EB2) presented an upregulation in mRNA expression of PD-L1 compared to excess of blasts 1 (MDS-EB1) (p = 0.050). Throughout the statistical analysis, we detected three patients with very high levels of PD-L1 expression, being classified as outliers. Analyzing these three patients specifically, all of them had hemoglobin lower than 8g/dL, blast count higher than 8%, dysplasia in at least two sectors and had died by the end of the study. The increase of PD-L1 in MDS may be considered a marker of poor prognosis.