Department of Pulmonary and Critical Care Medicine, Huadong Hospital, Fudan University, Shanghai, China.
Department of Oncology, Huashan Hospital, Fudan University, Shanghai, China.
Genomics. 2023 Jul;115(4):110648. doi: 10.1016/j.ygeno.2023.110648. Epub 2023 May 20.
Programmed death-ligand 1 (PD-L1) has been widely used in immunotherapy evaluation of patients with non-small cell lung cancer (NSCLC). However, the effect is not particularly ideal, and the association between PD-L1 and genetic alterations requires more exploration. Here, we performed targeted next-generation sequencing and PD-L1 immunohistochemistry (IHC) testing for PD-L1 expression on both tumor cells (TCs) and tumor-infiltrating immune cells (ICs) in 1549 patients. Our studies showed that surgical method of resection was positively correlated with IC+, and a low tumor mutation burden (TMB) was negatively correlated with TC+. Furthermore, we found that EGFR was mutually exclusive with both ALK and STK11. In addition, the features between PD-L1 expression status and genomic alterations were characterized. These results suggest that clinical characteristics and molecular phenotypes are associated with PD-L1 expression signatures, which may provide novel insights for improving the efficiency of immune checkpoint inhibitors (ICIs) in immunotherapy.
程序性死亡配体 1（PD-L1）已广泛应用于非小细胞肺癌（NSCLC）患者的免疫治疗评估。然而，其效果并不特别理想，PD-L1 与遗传改变之间的关联需要更多的探索。在这里，我们对 1549 例患者的肿瘤细胞（TCs）和肿瘤浸润免疫细胞（ICs）上的 PD-L1 表达进行了靶向下一代测序和 PD-L1 免疫组织化学（IHC）检测。我们的研究表明，切除的手术方法与 IC+呈正相关，低肿瘤突变负担（TMB）与 TC+呈负相关。此外，我们发现 EGFR 与 ALK 和 STK11 互斥。此外，还对 PD-L1 表达状态和基因组改变之间的特征进行了描述。这些结果表明，临床特征和分子表型与 PD-L1 表达特征相关，这可能为提高免疫检查点抑制剂（ICI）在免疫治疗中的效率提供新的见解。
