本研究旨在探讨 MDSC 在 CRC 免疫抑制中的关键作用，重点关注 CSF1R 和 JAK/STAT3 信号轴。此外，它还评估了 LNCs@CSF1R siRNA 和抗 PD-1 组合的治疗效果。来自 CRC 和邻近正常组织的单细胞转录组测序数据鉴定了 MDSC 相关的差异表达基因。 RNA-seq 分析全面分析了小鼠 CRC 肿瘤中的 MDSC 基因表达。 LNCs@CSF1R siRNA纳米载体有效靶向并抑制CSF1R。流式细胞术量化了 CSF1R 抑制后 MDSC 表面标记物的变化。 RNA-seq 和通路富集分析揭示了 CSF1R 对 MDSC 代谢和信号传导的影响。使用 Colivelin 和代谢评估验证了 CSF1R 抑制对 JAK/STAT3 信号轴的影响。通过基于荧光的流式细胞术测量葡萄糖和脂肪酸的摄取。 LNCs@CSF1R siRNA 和抗 PD-1 单独或联合使用的功效在小鼠 CRC 模型中通过广泛的肿瘤切片分析进行了评估。CSF1R 在 MDSC 介导的免疫抑制中发挥着重要作用。 LNCs@CSF1R siRNA纳米载体有效靶向MDSC并抑制CSF1R。 CSF1R通过JAK/STAT3信号轴调节MDSC脂肪酸代谢和免疫抑制。抑制 CSF1R 会降低 STAT3 的激活和靶基因的表达，而 Colivelin 可以挽救这一现象。 LNCs@CSF1R siRNA 和抗 PD-1 联合治疗显着减缓了肿瘤生长，并降低了 CRC 肿瘤内的 MDSC 丰度。CSF1R 通过 JAK/STAT3 轴关键性地调节 MDSC，特别是在脂肪酸代谢和免疫抑制方面。 LNCs@CSF1R siRNA 和抗 PD-1 联合治疗可增强小鼠 CRC 模型的治疗效果，为未来的临床应用奠定坚实的基础。© 2024。作者。

This study aimed to investigate the critical role of MDSCs in CRC immune suppression, focusing on the CSF1R and JAK/STAT3 signaling axis. Additionally, it assessed the therapeutic efficacy of LNCs@CSF1R siRNA and anti-PD-1 in combination.Single-cell transcriptome sequencing data from CRC and adjacent normal tissues identified MDSC-related differentially expressed genes. RNA-seq analysis comprehensively profiled MDSC gene expression in murine CRC tumors. LNCs@CSF1R siRNA nanocarriers effectively targeted and inhibited CSF1R. Flow cytometry quantified changes in MDSC surface markers post-CSF1R inhibition. RNA-seq and pathway enrichment analyses revealed the impact of CSF1R on MDSC metabolism and signaling. The effect of CSF1R inhibition on the JAK/STAT3 signaling axis was validated using Colivelin and metabolic assessments. Glucose and fatty acid uptake were measured via fluorescence-based flow cytometry. The efficacy of LNCs@CSF1R siRNA and anti-PD-1, alone and in combination, was evaluated in a murine CRC model with extensive tumor section analyses.CSF1R played a significant role in MDSC-mediated immune suppression. LNCs@CSF1R siRNA nanocarriers effectively targeted MDSCs and inhibited CSF1R. CSF1R regulated MDSC fatty acid metabolism and immune suppression through the JAK/STAT3 signaling axis. Inhibition of CSF1R reduced STAT3 activation and target gene expression, which was rescued by Colivelin. Combined treatment with LNCs@CSF1R siRNA and anti-PD-1 significantly slowed tumor growth and reduced MDSC abundance within CRC tumors.CSF1R via the JAK/STAT3 axis critically regulates MDSCs, particularly in fatty acid metabolism and immune suppression. Combined therapy with LNCs@CSF1R siRNA and anti-PD-1 enhances therapeutic efficacy in a murine CRC model, providing a strong foundation for future clinical applications.© 2024. The Author(s).