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切除的非小细胞肺癌中的 PD-L1 表达和肿瘤微环境模式。

PD-L1 Expression and Tumour Microenvironment Patterns in Resected Non-Small-Cell Lung Cancer.

机构信息

Department of Pulmonology, Medical Academy, Lithuanian University of Health Sciences, 44307 Kaunas, Lithuania.

Department of Pathology, Medical Academy, Lithuanian University of Health Sciences, 44307 Kaunas, Lithuania.

出版信息

Medicina (Kaunas). 2024 Mar 14;60(3):482. doi: 10.3390/medicina60030482.

Abstract

: Although perioperative immunotherapy is implemented as a standard of care for resected non-small cell lung cancer (NSCLC), there is unmet need for predictive biomarkers as programmed death-ligand 1 (PD-L1) is not the perfect one. The functionality of tumour-infiltrating immune cells in the tumour microenvironment (TME) and the involvement in immune system response is one of the crucial factors that lead to pro- or anti-tumourigenic role and could predict response to PD-1 and PD-L1 inhibitors. So, the investigation of PD-L1 expression in the context of TME in early stages of resected NSCLC is urgent required. : PD-L1 expression by three scoring methods: tumour proportion score (TPS), immune cell score (IC), and combined proportion score (CPS) was assessed in 72 archival tumour tissue specimens from stage I-III surgically resected NSCLC patients and associations with immune cells in TME were explored. : PD-L1 expression ≥1% evaluated by TPS, IC, and CPS was detected in 28%, 36%, and 39% of cases and moderate, substantial, and strong agreement between TPS and IC, TPS and CPS, CPS and IC was detected (Cohen's κ coefficient 0.556, 0.63, and 0.941, respectively). PD-L1 TPS, IC, and CPS correlated with smoking intensity defined as pack-years (r = 0.0305, = 0.012; r = 0.305, = 0.013, and r = 0.378, = 0.002, respectively). Only PD-L1 TPS was associated with squamous cell carcinoma ( = 0.028). PD-L1 IC ≥1% was more often seen in tumours with high CD4 T cells infiltration ( = 0.02), while PD-L1 CPS ≥1%-in tumours with high CD4 and CD8 T cells infiltration ( = 0.021 and = 0.048, respectively). PD-L1 IC and CPS ≥10% was more often detected in tumours with greater number of tumour-infiltrating CD4Foxp3 T cells ( = 0.01 and = 0.025, respectively). PD-L1 TPS ≥50% was associated with higher probability to detect greater number of tumour-infiltrating M2 macrophages ( = 0.021). No association was found between PD-L1 alone or in combination with tumour-infiltrating lymphocytes, macrophages, and disease-free or overall survival. : This study results revealed that rates of PD-L1 expression correlated among three scoring methods (TPS, IC, and CPS). Moreover, PD-L1 expression was significantly associated with smoking intensity, squamous histology, and tumour-infiltrating immune cells.

摘要

尽管围手术期免疫治疗已被实施为非小细胞肺癌(NSCLC)的标准治疗方法,但仍需要预测生物标志物,因为程序性死亡配体 1(PD-L1)并非完美的生物标志物。肿瘤浸润免疫细胞在肿瘤微环境(TME)中的功能及其在免疫系统反应中的参与是导致促肿瘤或抗肿瘤作用的关键因素之一,并可预测对 PD-1 和 PD-L1 抑制剂的反应。因此,迫切需要研究 PD-L1 在早期可切除 NSCLC 中的 TME 中的表达情况。本研究评估了 72 例 I-III 期手术切除 NSCLC 患者的 72 例存档肿瘤组织标本中三种评分方法(肿瘤比例评分(TPS)、免疫细胞评分(IC)和联合比例评分(CPS))的 PD-L1 表达情况,并探讨了其与 TME 中免疫细胞的相关性。通过 TPS、IC 和 CPS 评估 PD-L1 表达≥1%,在 28%、36%和 39%的病例中检测到,TPS 和 IC、TPS 和 CPS、CPS 和 IC 之间检测到中度、显著和强一致性(Cohen's κ 系数分别为 0.556、0.63 和 0.941)。PD-L1 TPS、IC 和 CPS 与吸烟强度(以包年定义)相关(r=0.0305,p=0.012;r=0.305,p=0.013,r=0.378,p=0.002)。仅 PD-L1 TPS 与鳞状细胞癌相关(p=0.028)。PD-L1 IC≥1%更常见于 CD4 T 细胞浸润高的肿瘤(p=0.02),而 PD-L1 CPS≥1%-则见于 CD4 和 CD8 T 细胞浸润高的肿瘤(p=0.021 和 p=0.048)。PD-L1 IC 和 CPS≥10%更常见于浸润 CD4Foxp3 T 细胞较多的肿瘤(p=0.01 和 p=0.025)。PD-L1 TPS≥50%与检测到更多 M2 巨噬细胞的可能性更高相关(p=0.021)。PD-L1 单独或与肿瘤浸润淋巴细胞、巨噬细胞及无病或总生存期无相关性。本研究结果表明,三种评分方法(TPS、IC 和 CPS)之间的 PD-L1 表达率相关。此外,PD-L1 表达与吸烟强度、鳞状组织学和肿瘤浸润免疫细胞显著相关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bf92/10972066/f29383b7da38/medicina-60-00482-g001.jpg

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