Holmström Morten Orebo, Riley Caroline Hasselbalch, Skov Vibe, Svane Inge Marie, Hasselbalch Hans Carl, Andersen Mads Hald
Department of Hematology, Zealand University Hospital, Roskilde, Denmark.
Center for Cancer Immune Therapy, Department of Hematology, Herlev Hospital, Copenhagen University Hospital, Herlev, Denmark.
Oncoimmunology. 2018 Feb 27;7(6):e1433521. doi: 10.1080/2162402X.2018.1433521. eCollection 2018.
The Chronic Myeloproliferative Neoplasms (MPN) are cancers characterized by hyperinflammation and immune deregulation. Concurrently, the expression of the immune check point programmed death ligand 1 (PD-L1) is induced by inflammation. In this study we report on the occurrence of spontaneous T cell responses against a PD-L1 derived epitope in patients with MPN. We show that 71% of patients display a significant immune response against PD-L1, and patients with advanced MPN have significantly fewer and weaker PD-L1 specific immune responses compared to patients with non-advanced MPN. The PD-L1 specific T cell responses are CD4 T cell responses, and by gene expression analysis we show that expression of PD-L1 is enhanced in patients with MPN. This could imply that the tumor specific immune response in MPN could be enhanced by vaccination with PD-L1 derived epitopes by boosting the anti-regulatory immune response hereby allowing tumor specific T cell to exert anti-tumor immunity.
慢性骨髓增殖性肿瘤（MPN）是以高度炎症和免疫失调为特征的癌症。同时，免疫检查点程序性死亡配体1（PD-L1）的表达由炎症诱导。在本研究中，我们报告了MPN患者中针对PD-L1衍生表位的自发T细胞反应的发生情况。我们发现71%的患者对PD-L1表现出显著的免疫反应，与非晚期MPN患者相比，晚期MPN患者的PD-L1特异性免疫反应明显更少且更弱。PD-L1特异性T细胞反应是CD4 T细胞反应，通过基因表达分析我们表明MPN患者中PD-L1的表达增强。这可能意味着通过用PD-L1衍生表位进行疫苗接种来增强抗调节免疫反应，从而使肿瘤特异性T细胞发挥抗肿瘤免疫，MPN中的肿瘤特异性免疫反应可能会得到增强。
