Similar programmed death ligand 1 (PD-L1) expression profile in patients with mild COPD and lung cancer.
Similar programmed death ligand 1 (PD-L1) expression profile in patients with mild COPD and lung cancer.
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DOI：
10.1038/s41598-022-26650-9
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发表时间：
2022-12-27
影响因子：
4.6
通讯作者：
中科院分区：
文献类型：
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程序性死亡配体1（PD-L1）在调节非小细胞肺癌（NSCLC）的免疫耐受中至关重要。肺泡巨噬细胞（AM）衍生的PD-L1与其受体PD-1结合，在监视淋巴细胞上，导致淋巴细胞耗竭。PD-L1表达增加与香烟烟雾（CS）暴露相关。然而，PD-L1在与NSCLC相关的CS相关肺部疾病（如慢性阻塞性肺疾病（COPD））中的作用仍不清楚。在患有COPD或NSCLC的曾经吸烟者以及曾经和从未吸烟者对照的两个不同队列中，我们评估了PD-L1表达：（1）通过福尔马林固定石蜡包埋（FFPE）肺组织切片（n = 19）的尖端数字空间蛋白质组学和转录组学分析（Geomx）;（2）通过支气管肺泡灌洗（BAL）AM的三重免疫荧光染色（n = 83）。还定量了暴露于CS浸提液的BAL AM中的PD-L1 mRNA表达。与重度-极重度（GOLD 3-4）COPD患者和对照组相比，轻度-中度（GOLD 1-2）COPD患者的细支气管壁、实质和血管壁中PD-L1表达增加。在所有COPD患者中，PD-L1蛋白表达与肿瘤进展相关基因的上调和抑癌基因的下调相关，并与FEV1%预测值密切直接相关，表明轻度COPD阶段的PD-L1表达高于重度COPD阶段。在细支气管中，PD-L1水平与功能活性AM的数量密切直接相关。在BAL中，我们证实来自GOLD 1-2 COPD和NSCLC患者的AM与所有其他组相比具有最高且相似的PD-L1表达水平，与主动吸烟无关。有趣的是，与轻度COPD患者相比，更严重COPD患者的AM PD-L1表达减少。急性CS提取物刺激仅在从不吸烟的AM中增加PD-L1 mRNA表达，而在曾经吸烟的AM中则没有。与重度COPD患者和对照相比，轻度COPD和NSCLC患者的肺的特征在于细支气管和功能活性AM中类似的强PD-L1表达特征。主动吸烟不会影响PD-L1水平。这些观察结果代表了理解COPD和肺癌发病和进展之间联系的先天免疫机制的新资源，并为未来研究CS促进肿瘤发生和COPD的机制铺平了道路。
Programmed Death Ligand 1 (PD-L1) is crucial in regulating the immunological tolerance in non-small cell lung cancer (NSCLC). Alveolar macrophage (AM)-derived PD-L1 binds to its receptor, PD-1, on surveilling lymphocytes, leading to lymphocyte exhaustion. Increased PD-L1 expression is associated with cigarette smoke (CS)-exposure. However, the PD-L1 role in CS-associated lung diseases associated with NSCLC, such as chronic obstructive pulmonary disease (COPD), is still unclear. In two different cohorts of ever smokers with COPD or NSCLC, and ever and never smoker controls, we evaluated PD-L1 expression: (1) via cutting-edge digital spatial proteomic and transcriptomic profiling (Geomx) of formalin-fixed paraffin-embedded (FFPE) lung tissue sections (n = 19); and (2) via triple immunofluorescence staining of bronchoalveolar lavage (BAL) AMs (n = 83). PD-L1 mRNA expression was also quantified in BAL AMs exposed to CS extract. PD-L1 expression was increased in the bronchiolar wall, parenchyma, and vascular wall from mild-moderate (GOLD 1–2) COPD patients compared to severe-very severe (GOLD 3–4) COPD patients and controls. Within all the COPD patients, PD-L1 protein expression was associated with upregulation of genes involved in tumor progression and downregulation of oncosuppressive genes, and strongly directly correlated with the FEV1% predicted, indicating higher PD-L1 expression in the milder vs. more severe COPD stages. In bronchioles, PD-L1 levels were strongly directly correlated with the number of functionally active AMs. In BAL, we confirmed that AMs from patients with both GOLD 1–2 COPD and NSCLC had the highest and similar, PD-L1 expression levels versus all the other groups, independently from active cigarette smoking. Intriguingly, AMs from patients with more severe COPD had reduced AM PD-L1 expression compared to patients with mild COPD. Acute CS extract stimulation increased PD-L1 mRNA expression only in never-and not in ever-smoker AMs. Lungs from patients with mild COPD and NSCLC are characterized by a similar strong PD-L1 expression signature in bronchioles and functionally active AMs compared to patients with severe COPD and controls. Active smoking does not affect PD-L1 levels. These observations represent a new resource in understanding the innate immune mechanisms underlying the link between COPD and lung cancer onset and progression and pave the way to future studies focused on the mechanisms by which CS promotes tumorigenesis and COPD.
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影响因子：
13.6
作者：
Martin-Cofreces NB;Chichon FJ;Calvo E;Torralba D;Bustos-Moran E;Dosil SG;Rojas-Gomez A;Bonzon-Kulichenko E;Lopez JA;Otón J;Sorrentino A;Zabala JC;Vernos I;Vazquez J;Valpuesta JM;Sanchez-Madrid F
通讯作者：
Sanchez-Madrid F
DOI：
10.1038/nrc3239
发表时间：
2012-03-22
期刊：
Nature reviews. Cancer
影响因子：
--
作者：
Pardoll DM
通讯作者：
Pardoll DM
组蛋白甲基转移酶KMT5A基因体外调节甲状腺乳头状癌的肿瘤发生和脂质代谢
影响因子：
4.2
作者：
Liao, Tian;Wang, Yuan-Jin;Ji, Qing-Hai
通讯作者：
Ji, Qing-Hai
影响因子：
7.3
作者：
Heming M;Gran S;Jauch SL;Fischer-Riepe L;Russo A;Klotz L;Hermann S;Schäfers M;Roth J;Barczyk-Kahlert K
通讯作者：
Barczyk-Kahlert K
DOI：
10.1164/rccm.200509-1461oc
发表时间：
2006-07-01
影响因子：
24.7
作者：
Berenson, Charles S.;Wrona, Catherine T.;Sethi, Sanjay
通讯作者：
Sethi, Sanjay