Departments of Orthopedics, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 17 Nanli, Panjiayuan, Chaoyang District, Beijing, 100021, China.
Department of Orthopedics, Peking University First Hospital, Beijing, 100021, China.
J Cancer Res Clin Oncol. 2024 Jul 20;150(7):356. doi: 10.1007/s00432-024-05787-2.
Neoadjuvant chemotherapy serves as an effective strategy for treating osteosarcoma (OS) not only by targeting cancerous cells but also by influencing the tumor's immune and stromal elements. Gaining insights into how chemotherapy reshapes the tumor's local environment is crucial for advancing OS treatment protocols.
Using single-cell RNA sequencing, this study analyzed tumor samples from patients with advanced osteosarcoma collected both before and after chemotherapy.
The results revealed that chemotherapy caused the remaining OS cells to express higher levels of genes associated with stemness. Additionally, this process enhances the presence of cancer-associated fibroblasts, increasing their ability to modify the extracellular matrix (ECM). Chemotherapy also increases the number of endothelial cells, albeit with compromised differentiation capabilities. Importantly, the treatment reduced the immune cell population, including myeloid and T/NK cells, particularly impacting the subpopulations with tumor-fighting capabilities.
These findings highlight the complex reaction of the tumor environment to chemotherapy, providing valuable insights into how chemotherapy influences OS cells and the tumor microenvironment (TME). This knowledge is essential for understanding OS resistance mechanisms to treatments, potentially guiding the development of novel therapies for managing advanced OS.
新辅助化疗不仅通过靶向癌细胞，还通过影响肿瘤的免疫和基质成分，成为治疗骨肉瘤（OS）的有效策略。深入了解化疗如何重塑肿瘤的局部环境对于推进 OS 治疗方案至关重要。
本研究使用单细胞 RNA 测序技术，分析了来自接受化疗的晚期骨肉瘤患者的肿瘤样本，这些样本在化疗前后均有采集。
结果表明，化疗导致剩余的 OS 细胞表达更高水平与干性相关的基因。此外，这一过程增强了癌相关成纤维细胞的存在，增加了它们修饰细胞外基质（ECM）的能力。化疗还增加了内皮细胞的数量，但分化能力受损。重要的是，治疗降低了免疫细胞群体，包括髓系和 T/NK 细胞，特别是对具有抗肿瘤能力的亚群影响较大。
这些发现强调了肿瘤环境对化疗的复杂反应，为我们提供了宝贵的见解，了解化疗如何影响 OS 细胞和肿瘤微环境（TME）。这些知识对于理解 OS 对治疗的耐药机制至关重要，可能为管理晚期 OS 提供新的治疗方法。
