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High PD-1 expression on regulatory and effector T-cells in lung cancer draining lymph nodes

机译:PD-1在肺癌引流淋巴结中对调节性T细胞和效应T细胞的高表达

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The treatment of advanced nonsmall cell lung cancer (NSCLC) with PD-1/PD-L1 immune checkpoint inhibitors has improved clinical outcome for a proportion of patients. The current challenge is to find better biomarkers than PD-L1 immunohistochemistry (IHC) that will identify patients likely to benefit from this therapy. In this exploratory study we assessed the differences in T-cell subsets and PD-1 expression levels on T-cells in tumour-draining lymph nodes (TDLNs) and peripheral blood mononuclear cells (PBMCs).To evaluate this, flow cytometric analyses were performed on endobronchial ultrasound-guided (EBUS) fine-needle aspirates (FNA) from TDLNs of patients with NSCLC, and the results were compared to paired PBMC samples. For a select number of patients, we were also able to obtain cells from a non-TDLN (NTDLN) sample.Our data show that the frequency of PD-1+ CD4+ and CD8+ T-cells, as well as the PD-1 expression level on activated regulatory T (aTreg) and CD4+ and CD8+ T-cells, are higher in TDLNs than in PBMCs and, in a small sub-analysis, NTDLNs.These elevated PD-1 expression levels in TDLNs may reflect tumour-specific T-cell priming and conditioning, and may serve as a predictive or early-response biomarker during PD-1 checkpoint blockade.PD-1 in NSCLC tumour-draining lymph nodes as a potential biomarker http://ow.ly/QedU30bqJ6d
机译:用PD-1 / PD-L1免疫检查点抑制剂治疗晚期非小细胞肺癌(NSCLC),已改善了部分患者的临床结局。当前的挑战是找到比PD-L1免疫组织化学(IHC)更好的生物标记物,以识别可能从该疗法中受益的患者。在这项探索性研究中,我们评估了肿瘤引流淋巴结(TDLN)和外周血单个核细胞(PBMC)中T细胞的T细胞亚群和PD-1表达水平的差异。为此,进行了流式细胞分析对NSCLC患者的TDLN进行支气管内超声引导(EBUS)细针抽吸(FNA),并将结果与​​成对的PBMC样本进行比较。对于一定数量的患者,我们还能够从非TDLN(NTDLN)样本中获得细胞。我们的数据显示,PD-1 + CD4 +和CD8 + T细胞的频率以及PD-1的表达在TDLN中,激活的调节性T(aTreg)和CD4 +和CD8 + T细胞的水平高于PBMC,在较小的子分析中,NTDLNs也较高。这些TDLNs中PD-1表达水平的升高可能反映了肿瘤特异性T-细胞启动和调节,并可能在PD-1检查点封锁期间充当预测性或早期反应生物标志物。NSCLC肿瘤引流淋巴结中的PD-1作为潜在生物标志物

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