Sampaio Leticia Rodrigues, Viana Mateus de Aguiar, de Oliveira Vanessa Silva, Ferreira Bruna Vitoriano, Melo Mayara Magna Lima, de Oliveira Roberta Taiane Germano, Borges Daniela de Paula, Magalhãesa Silvia Maria Meira, Pinheiro Ronald F
Universidade Federal do Ceará (UFC), Fortaleza, CE, Brazil; Núcleo de Pesquisa e Desenvolvimento de Medicamentos (NPDM), Fortaleza, CE, Brazil.
Universidade Federal do Ceará (UFC), Fortaleza, CE, Brazil; Núcleo de Pesquisa e Desenvolvimento de Medicamentos (NPDM), Fortaleza, CE, Brazil.
Hematol Transfus Cell Ther. 2024 Apr-Jun;46(2):146-152. doi: 10.1016/j.htct.2023.05.002. Epub 2023 Jun 5.
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.
免疫检查点是免疫系统反应的调节因子，可实现自我耐受。程序性细胞死亡蛋白1（PD-1）及其配体（PD-L1）等分子通过淋巴细胞反应的共抑制信号参与免疫检查点。在癌症中，PD-L1表达与免疫逃逸机制相关，这有利于肿瘤生长。抗PD-1/PD-L1药物在实体瘤中的应用已得到充分描述，但在血液系统恶性肿瘤中仍未完全了解。骨髓增生异常综合征（MDS）是异质性骨髓疾病，进展为急性髓系白血病（AML）的风险增加。MDS影响造血干细胞，其发病机制除免疫失调外，还与遗传和表观遗传缺陷有关。PD-L1对MDS的影响尚不清楚。
在本研究中，我们评估了53例根据世界卫生组织2016年分类法分类的MDS患者中PD-L1的mRNA表达。
红系造血异常的患者PD-L1表达明显高于无红系造血异常的患者（p = 0.050）。与伴有过多原始细胞1型的MDS（MDS-EB1）相比，伴有过多原始细胞2型的MDS（MDS-EB2）患者的PD-L1 mRNA表达显著上调（p = 0.050）。此外，我们检测到3例PD-L1表达水平非常高的患者，经统计学分类为异常值。
我们认为，PD-L1的高表达与MDS的预后较差有关，有必要进行功能研究以评估抗PD-L1疗法在高危MDS（如MDS-EB）中的可能应用。
