The Second School of Clinical Medicine, Southern Medical University, Guangzhou, China.
Guangdong Lung Cancer Institute, Medical Research Center, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.
Thorac Cancer. 2022 Jul;13(13):1948-1960. doi: 10.1111/1759-7714.14473. Epub 2022 May 20.
Brain metastases (BM) are common in lung cancer. However, data on the status of immune biomarkers in BM lesions remain limited.
We retrospectively analyzed PD-L1 expression and infiltration levels of CD3 , CD4 , CD8 T cells as biomarkers by immunohistochemistry in both BM lesions and primary lung cancer (PL) lesions of 29 lung cancer (LC) patients. In addition, the correlations between these biomarkers and the clinical outcome were analyzed using log-rank test.
Intratumoral heterogeneous expression of PD-L1 was observed on tumor cells (TCs) in 11 cases and on immune cells (ICs) in 10 cases with BM samples from multiple regions. There was a disagreement in PD-L1 expression on TCs between paired BM and PL lesions in 15 cases and on ICs in seven cases. Intraepithelial CD3 and CD8 T cell infiltration levels in BM samples were lower than those in the paired PL samples. PD-L1 positivity on both TCs and ICs was associated with a better post-BM-surgery prognosis (p = 0.010; p = 0.041). Notably, PD-L1 positivity on TCs and a high level of intraepithelial CD8 T cell infiltration could serve as an integrated biomarker that indicates longer survival time (p = 0.004) in LC patients.
The heterogeneity in PD-L1 expression was common in both stromal and intraepithelial regions in BM lesions of LC patients, suggesting the need for multiregional PD-L1 testing in clinical practice. More importantly, a combination of PD-L1 expression on TCs with intraepithelial CD8 T cell infiltration might predict better post-BM-surgery outcomes.
脑转移（BM）在肺癌中很常见。然而，关于 BM 病变中免疫生物标志物状态的数据仍然有限。
我们通过免疫组织化学法，回顾性分析了 29 例肺癌（LC）患者的 BM 病变和原发性肺癌（PL）病变中 PD-L1 表达和 CD3、CD4、CD8 T 细胞浸润水平作为生物标志物。此外，使用对数秩检验分析了这些生物标志物与临床结局之间的相关性。
11 例 BM 样本的肿瘤细胞（TCs）和 10 例 BM 样本的免疫细胞（ICs）中观察到 PD-L1 的肿瘤内异质性表达。15 例 BM 和 PL 配对病变中 PD-L1 在 TCs 上的表达存在不一致，7 例 BM 和 PL 配对病变中 PD-L1 在 ICs 上的表达存在不一致。BM 样本中上皮内 CD3 和 CD8 T 细胞浸润水平低于配对 PL 样本。TCs 和 ICs 上 PD-L1 阳性与 BM 手术后预后较好相关（p=0.010；p=0.041）。值得注意的是，TCs 上 PD-L1 阳性和上皮内 CD8 T 细胞浸润水平较高可作为一个综合生物标志物，表明 LC 患者的生存时间更长（p=0.004）。
LC 患者 BM 病变中 PD-L1 表达在基质和上皮内区域均存在异质性，提示在临床实践中需要进行多区域 PD-L1 检测。更重要的是，TCs 上 PD-L1 表达与上皮内 CD8 T 细胞浸润相结合可能预测 BM 手术后的更好结局。
