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高 PD-L1 表达与免疫抑制性肿瘤免疫微环境相关,并与 -重排非小细胞肺癌的预后更差相关。

High PD-L1 Expression Correlates with an Immunosuppressive Tumour Immune Microenvironment and Worse Prognosis in -Rearranged Non-Small Cell Lung Cancer.

机构信息

Department of Pulmonary and Critical Care Medicine, Lung Cancer Center, West China Hospital, Sichuan University, Precision Medicine Key Laboratory of Sichuan Province, Chengdu 610041, China

出版信息

Biomolecules. 2023 Jun 15;13(6):991. doi: 10.3390/biom13060991.

Abstract

High tumour programmed cell death-ligand 1 (PD-L1) expression is associated with poor progression-free survival (PFS) after tyrosine kinase inhibitor (TKI) therapy in -rearranged non-small cell lung cancer (NSCLC). However, the characteristics of the tumour microenvironment (TME) and their prognostic values in -rearranged NSCLC are unknown. Here, we collected tumour tissues from pretreated -rearranged NSCLC patients, immunohistochemical staining was used to assess PD-L1 expression, and tumour-infiltrating immune cells were determined via multiplex immunofluorescence staining (mIF). Our data showed that the median values of PFS for the high PD-L1 group and low PD-L1 group who received ALK-TKI treatment were 4.4 and 16.4 months, respectively ( = 0.008). The median overall survival (OS) of the two groups was 24.0 months and not reached, respectively ( = 0.021). Via univariate and multivariate analyses, a high PD-L1 expression and a worse ECOG PS were determined to be independent prognostic factors of OS (HR = 3.35, 95% CI: 1.23-9.11, = 0.018; HR = 6.42, 95% CI: 1.45-28.44, = 0.014, respectively). In addition, the high PD-L1 group had increased Tregs and exhausted CD8+ T cells in both the tumour and stroma (all < 0.05). High PD-L1 expression was an adverse predictive and prognostic biomarker for -rearranged NSCLC. The characteristics of the TME in patients with high PD-L1 expression were shown to have an immunosuppressive status.

摘要

高肿瘤程序性死亡配体 1(PD-L1)表达与间变性淋巴瘤激酶(ALK)重排的非小细胞肺癌(NSCLC)患者接受酪氨酸激酶抑制剂(TKI)治疗后的无进展生存期(PFS)不良相关。然而,ALK 重排 NSCLC 中肿瘤微环境(TME)的特征及其预后价值尚不清楚。在此,我们收集了预处理的 ALK 重排 NSCLC 患者的肿瘤组织,通过免疫组织化学染色评估 PD-L1 表达,并通过多重免疫荧光染色(mIF)测定肿瘤浸润免疫细胞。我们的数据显示,接受 ALK-TKI 治疗的高 PD-L1 组和低 PD-L1 组的中位 PFS 值分别为 4.4 个月和 16.4 个月(=0.008)。两组的中位总生存期(OS)分别为 24.0 个月和未达到(=0.021)。通过单因素和多因素分析,高 PD-L1 表达和较差的 ECOG PS 被确定为 OS 的独立预后因素(HR=3.35,95%CI:1.23-9.11,=0.018;HR=6.42,95%CI:1.45-28.44,=0.014)。此外,高 PD-L1 组的肿瘤和基质中 Tregs 和耗竭的 CD8+T 细胞均增加(均<0.05)。高 PD-L1 表达是 ALK 重排 NSCLC 的不良预测和预后生物标志物。高 PD-L1 表达患者的 TME 特征显示出免疫抑制状态。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c662/10296689/e0c8db4977a9/biomolecules-13-00991-g001.jpg

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