Single-cell transcriptomic insights into chemotherapy-induced remodeling of the osteosarcoma tumor microenvironment

单细胞转录组学洞察化疗引起的骨肉瘤肿瘤微环境重塑

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作者:Xuejing Zheng #, Wence Wu #, Zhenguo Zhao #, Xinxin Zhang #, Shengji Yu

Conclusion

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.

Methods

Using single-cell RNA sequencing, this study analyzed tumor samples from patients with advanced osteosarcoma collected both before and after chemotherapy.

Purpose

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.

Results

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.

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