Institute of Respiratory Health, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, China.
Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, China.
Int J Cancer. 2023 Sep 15;153(6):1273-1286. doi: 10.1002/ijc.34629. Epub 2023 Jun 19.
Chemotherapy is the standard therapy for small cell lung cancer (SCLC), but relapse is common and the 2-year survival rate remains low. Given the contribution of the tumor microenvironment (TME) to cancer development and response to treatment, we analyzed here how chemotherapy alters the TME in SCLC using single-cell RNA sequencing. The comparison between neuroendocrine cells and other epithelial cells in five chemotherapy-naive patients identified upregulation of Notch-inhibiting genes, such as DLL3 and HES6. Analysis of genes differentially expressed between five patients receiving chemotherapy and five treatment-naive patients in cells in the TME showed that chemotherapy promoted antigen presentation and senescence in neuroendocrine cells, upregulated ID1 to enhance angiogenic activities of stalk-like endothelial cells and strengthened vascular endothelial growth factor signaling in lymphatic endothelial cells. Chemotherapy also promoted the remodeling of extracellular matrix by fibroblasts and upregulated interferon-mediated antitumor immune responses by B and T cells. Our single-cell transcriptome analysis provides insights into how chemotherapy affects the TME in SCLC, which may guide efforts to make therapy more effective.
化疗是小细胞肺癌（SCLC）的标准疗法，但复发很常见，2 年生存率仍然较低。鉴于肿瘤微环境（TME）对癌症发展和治疗反应的贡献，我们在这里使用单细胞 RNA 测序分析了化疗如何改变 SCLC 中的 TME。在五名未经化疗的患者中，神经内分泌细胞与其他上皮细胞之间的比较鉴定出 Notch 抑制基因（如 DLL3 和 HES6）的上调。在 TME 中的细胞中，对五名接受化疗的患者和五名未经治疗的患者之间差异表达的基因进行分析表明，化疗促进了神经内分泌细胞的抗原呈递和衰老，上调了 ID1 以增强 stalk-like 内皮细胞的血管生成活性，并增强了淋巴管内皮细胞中的血管内皮生长因子信号传导。化疗还通过成纤维细胞促进细胞外基质的重塑，并通过 B 和 T 细胞上调干扰素介导的抗肿瘤免疫反应。我们的单细胞转录组分析提供了关于化疗如何影响 SCLC 中 TME 的见解，这可能有助于提高治疗效果。
