No.2 Department of Thoracic Surgery, Beijing Tuberculosis and Thoracic Tumor Research Institute/Beijing Chest Hospital, Capital Medical University, Beijing, China.
Department of Oncology, Tongren People’s Hospital, Tongren, Guizhou, China.
Aging (Albany NY). 2024 Jun 13;16(12):10348-10365. doi: 10.18632/aging.205932.
Exploring the molecular mechanisms of PD-1/PDL-1 blockade for non-small cell lung cancer (NSCLC) would facilitate understanding for tumor microenvironment (TME) and development of individualized medicine. To date, biomarkers of response to PD-1 blockade therapy were still limited. In this study, we hypothesize that cell type in the tumor microenvironment can influence the effect of PD-1 blockade immunotherapy through specific genes. Therefore, we re-analyze the single-cell RNA sequencing data and validation in tissue from lung adenocarcinoma patients. Dynamic changes of cellular subpopulation were observed after anti-PD-1 immunotherapy among TMEs between primary/metastasis or good/poor response patients. Non-exhausted CD8 T cells and dysregulated genes were observed in responsing patients from PD-1 blockade therapy. Among all changed genes, JUN, involved in PD-1 blockade immunotherapy pathway, and could be considered as a PD-1 responsing biomarker.
探索 PD-1/PDL-1 阻断在非小细胞肺癌 (NSCLC) 中的分子机制将有助于了解肿瘤微环境 (TME) 和个体化医学的发展。迄今为止，对 PD-1 阻断治疗反应的生物标志物仍然有限。在这项研究中，我们假设肿瘤微环境中的细胞类型可以通过特定基因影响 PD-1 阻断免疫治疗的效果。因此，我们重新分析了来自肺腺癌患者的组织中的单细胞 RNA 测序数据和验证。在原发性/转移性或良好/不良反应患者的 TME 中，观察到抗 PD-1 免疫治疗后细胞亚群的动态变化。在 PD-1 阻断治疗中，有反应的患者中观察到非耗竭的 CD8 T 细胞和失调的基因。在所有变化的基因中，参与 PD-1 阻断免疫治疗途径的 JUN 可以被认为是 PD-1 反应的生物标志物。
