由于治疗选择有限和死亡率高，解决癌症脑转移面临着巨大的挑战。在临床实践中，中医药与其他治疗方式的结合在控制疾病进展和提高生活质量方面表现出显着的疗效。 SFI增强了免疫检查点抑制剂的抗肿瘤作用，重点研究了SFI作用的机制。最初，我们使用立体定位仪在C57BL/6小鼠中建立了B16-F10脑移植肿瘤模型。通过体内成像技术、HE染色和免疫荧光评估药物的疗效。采用质谱细胞术（CyTOF）和流式细胞术分析SFI对肿瘤微环境中免疫细胞亚群的影响。随后，利用转录组测序和代谢组学研究 SFI 对黑色素瘤相关基因和代谢的影响。通过分子对接、Western Blot 和 ELISA 检测来研究 SFI 干预黑色素瘤脂肪酸代谢的靶点。最后，在脑移植肿瘤模型中研究了SFI联合免疫检查点抑制剂的抗肿瘤作用。药理学研究结果表明，SFI以剂量依赖性方式抑制黑色素瘤脑移植肿瘤的生长。 CyTOF、流式细胞术和免疫荧光结果显示，SFI 显着降低肿瘤微环境中骨髓源性抑制细胞 (MDSC) 和调节性 T 细胞 (Treg) 的水平，同时提高 CD8 T 和 CD4 T 细胞的水平。随后，体外和体内的转录组学和代谢组学研究结果表明，SFI 显着抑制黑色素瘤细胞中的花生四烯酸代谢过程。分子对接和生物学实验表明，SFI抑制D6D的表达和COX-2的活性，导致下游PGE2产量减少。最后，SFI显着增强PD-L1抗体对颅内黑色素瘤的抗肿瘤作用。SFI通过干预脂肪酸代谢改善黑色素瘤的肿瘤免疫微环境，从而降低MDSCs和Tregs的水平，同时增加CD8 T和CD4 T的水平细胞。最终，这种增强会增强免疫检查点抑制剂 PD-L1 抗体的抗肿瘤作用。版权所有 © 2023 Elsevier GmbH。版权所有。

Addressing brain metastases in cancer presents substantial challenges due to limited therapeutic options and high mortality rates. In clinical practice, the amalgamation of traditional Chinese medicine with other treatment modalities has exhibited noteworthy efficacy in managing disease progression and enhancing quality of life.To substantiate the regulatory effects of Shenqi Fuzheng Injection (SFI) on the microenvironment of melanoma brain metastases and appraise whether SFI augments the anti-tumour effects of immune checkpoint inhibitors, with a specific focus on investigating the mechanisms underlying SFI's actions.Initially, we established a B16-F10 brain transplant tumour model in C57BL/6 mice using a stereotaxic apparatus. The efficacy of the drug was evaluated through in vivo imaging technology, HE staining, and immunofluorescence. Mass Cytometry (CyTOF) and flow cytometry were employed to analyse the impact of SFI on immune cell subpopulations in the tumour microenvironment. Subsequently, transcriptome sequencing and metabolomics were utilised to examine the effects of SFI on melanoma-related genes and metabolism. Molecular docking, Western Blot, and ELISA assays were conducted to investigate the targets of SFI in intervening in melanoma fatty acid metabolism. Finally, the anti-tumour effects of SFI in combination with immune checkpoint inhibitors were scrutinised in the brain transplant tumour model.The pharmacological findings demonstrated that SFI inhibits the growth of melanoma brain transplant tumours in a dose-dependent manner. CyTOF, flow cytometry, and immunofluorescence results revealed that SFI significantly diminishes the levels of Myeloid-Derived Suppressor Cells (MDSCs) and Regulatory T cells (Tregs) in the tumour microenvironment while enhancing the levels of CD8+T and CD4+ T cells. Subsequently, transcriptomic and metabolomic findings, both in vitro and in vivo, indicate that SFI significantly inhibits the arachidonic acid metabolism process in melanoma cells. Molecular docking and biological experiments showed that SFI inhibits the expression of D6D and the activity of COX-2, leading to a reduction in downstream PGE2 production. Lastly, SFI significantly enhances the anti-tumour effects of PD-L1 antibody against intracranial melanoma.SFI improves the tumour immune microenvironment in melanoma by intervening in fatty acid metabolism, thereby reducing levels of MDSCs and Tregs while increasing levels of CD8+ T and CD4+ T cells. Ultimately, this augmentation leads to enhanced anti-tumour effects of the immune checkpoint inhibitor PD-L1 antibody.Copyright © 2023 Elsevier GmbH. All rights reserved.