Jovanovic Dragana, Roksandic Milenkovic Marina, Kotur Stevuljevic Jelena, Markovic Jelena, Ceriman Vesna, Kontic Milica, Skodric Trifunovic Vesna
University Hospital of Pulmonology, Clinical Center of Serbia, Belgrade, Serbia.
School of Medicine, University of Belgrade, Belgrade, Serbia.
J Thorac Dis. 2018 Dec;10(12):6660-6669. doi: 10.21037/jtd.2018.11.16.
Idiopathic pulmonary fibrosis (IPF) has common risk factors with cancer and significant similarities in the pathobiology process, both diseases having poor outcomes. Immune checkpoint PD-L1 has become the target of checkpoint inhibitory therapy that unleashes antitumor T cells and has revolutionized cancer treatment. This is a pilot study exploring membrane immune checkpoint PD-L1 expression in human IPF lung tissue samples and its soluble form, soluble PD-L1 (sPD-L1) plasma concentrations in IPF patients, in order to investigate potential role of PD-L1 as an IPF biomarker.
Twelve human IPF lung tissue samples (formalin-fixed, paraffin-embedded) obtained by surgical biopsy, have been tested for PD-L1 expression by PD-L1 IHC 22C3 pharmDx assay, while plasma samples for examination of sPD-L1 forms, PD-L1 (B7-H1/CD274) blood concentration, originated from 23 patients with IPF who did not undergo surgical biopsy.
Membrane PD-L1 expression in IPF lung tissue samples was positive to overexpression of PD-L1 in 9 samples out of 12. Only very few cells in the interstitium have shown a discrete PD-L1 expression, but not of a membrane type. As for sPD-L1 forms, we have found elevated concentrations of sPD-L1 in the serum of IPF patients 314.3 ng/L (117.7-483.1 ng/L), significantly higher compared with healthy control group 91.0 ng/L (52.4-119.7 ng/L), P<0.01.
For IPF with PD-L1 expression on alveolar macrophages, further studies are necessary to elucidate this phenomenon. Serum sPD-1/PD-L1 is easily detected in clinical practice and should be further evaluated as a potential prognostic or/and predictive biomarker in IPF.
特发性肺纤维化（IPF）与癌症具有共同的危险因素，并且在病理生物学过程中有显著相似性，两种疾病的预后均较差。免疫检查点PD-L1已成为释放抗肿瘤T细胞的检查点抑制疗法的靶点，并彻底改变了癌症治疗方式。这是一项探索人IPF肺组织样本中膜免疫检查点PD-L1表达及其可溶性形式、IPF患者血浆中可溶性PD-L1（sPD-L1）浓度的初步研究，以调查PD-L1作为IPF生物标志物的潜在作用。
通过手术活检获得的12份人IPF肺组织样本（福尔马林固定、石蜡包埋），采用PD-L1 IHC 22C3 pharmDx检测法检测PD-L1表达，而用于检测sPD-L1形式、PD-L1（B7-H1/CD274）血浓度的血浆样本，来自23例未接受手术活检的IPF患者。
IPF肺组织样本中的膜PD-L1表达在12份样本中有9份呈PD-L1阳性至过表达。间质中只有极少数细胞显示出离散的PD-L1表达，但不是膜型。至于sPD-L1形式，我们发现IPF患者血清中sPD-L1浓度升高，为314.3 ng/L（117.7 - 483.1 ng/L），与健康对照组91.0 ng/L（52.4 - 119.7 ng/L）相比显著更高，P<0.01。
对于肺泡巨噬细胞上有PD-L1表达的IPF，需要进一步研究以阐明这一现象。血清sPD-1/PD-L1在临床实践中易于检测，应进一步评估其作为IPF潜在预后或/和预测生物标志物的价值。
