研究动态
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高PD-L1表达与骨髓增生异常综合征的不利临床特征相关。

High PD-L1 expression is associated with unfavorable clinical features in myelodysplastic neoplasms.

发表日期:2023 Jun 05
作者: Leticia Rodrigues Sampaio, Mateus de Aguiar Viana, Vanessa Silva de Oliveira, Bruna Vitoriano Ferreira, Mayara Magna Lima Melo, Roberta Taiane Germano de Oliveira, Daniela de Paula Borges, Silvia Maria Meira Magalhãesa, Ronald F Pinheiro
来源: Epigenetics & Chromatin

摘要:

免疫检查点是调节免疫系统应答并实现自身耐受的调节因子。分子如程序细胞死亡蛋白1(PD-1)和其配体(PD-L1)通过信号传导共抑制淋巴细胞应答,参与免疫检查点。在癌症中,PD-L1表达与免疫逃避机制相关联,从而促进肿瘤生长。抗PD-1/PD-L1药物已在固体肿瘤中得到充分描述,但在血液系统恶性肿瘤中尚未完全理解。骨髓增生异常综合征(MDS)是一种骨髓异质性疾病,具有进展为急性髓系白血病(AML)的风险增加。MDS影响造血干细胞,其发病机制与遗传和表观遗传缺陷以及免疫调节失调有关。PD-L1对MDS的影响尚不清楚。在本研究中,我们评估了53例按2016年世界卫生组织(WHO)分类的MDS患者的PD-L1 mRNA表达情况。发现与无红细胞生成障碍的患者相比,具有无效红细胞生成的患者PD-L1表达显著增高(p=0.050)。MDS伴有爆发过多1(MDS-EB1)与MDS伴有爆发过多2(MDS-EB2)的患者与MDS-EB1相比,显示出mRNA PD-L1表达显著上调(p=0.050)。此外,我们发现三名患者PD-L1表达水平极高,被统计为异常值。我们认为PD-L1的高表达与MDS的预后较差有关,需要进行功能研究以评估抗PD-L1治疗在高危MDS(如MDS-EBs)中的潜在应用。版权 © 2023. Elsevier España, S.L.U. 发表。
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 use of anti-PD-1/PD-L1 drugs is already well described in solid tumors, but still not fully understood in hematologic malignancies. Myelodysplastic neoplasms (MDSs) are heterogeneous bone marrow disorders with an increased risk of progression to Acute Myeloid Leukemia (AML). The MDS affects hematopoietic stem cells and its pathogenesis is linked to genetic and epigenetic defects, in addition to immune dysregulation. The influence of the PD-L1 on the MDS remains unknown.In this study, we evaluated the mRNA expression of the PD-L1 in 53 patients with MDS, classified according to the WHO 2016 Classification.Patients with dyserythropoiesis presented significantly higher PD-L1 expression than patients without dyserythropoiesis (p = 0.050). Patients classified as having MDS with an excess of blasts 2 (MDS-EB2) presented a significant upregulation in the mRNA expression of the PD-L1 compared to the MDS with an excess of blasts 1 (MDS-EB1) (p = 0.050). Furthermore, we detected three patients with very high levels of PD-L1 expression, being statistically classified as outliers.We suggested that the high expression of the PD-L1 is associated with a worse prognosis in the MDS and functional studies are necessary to evaluate the possible use of anti-PD-L1 therapies for high-risk MDS, such as the MDS-EBs.Copyright © 2023. Published by Elsevier España, S.L.U.