经改良的补肾益气方（MBYF）已显示出作为抗PD-1的草药联合疗法在肺癌患者中的疗效。然而，MBYF在肺癌中的抗肿瘤作用机制尚不清楚。本研究旨在观察MBYF的抗肿瘤效应，并探究其与抗PD-1联合应用在肿瘤免疫微环境中的协同机制。通过评估Lewis肺癌（LLC）携带小鼠的肿瘤体积、重量和组织学来评估MBYF的抗肿瘤效应，共设五组（模型对照组、MBYF 8.125 g/kg组、MBYF 16.25 g/kg组、MBYF 32.50 g/kg组、抗PD-1组）。通过药理网络和肿瘤RNA测序进行机制分析，通过流式细胞术和免疫组化技术测量肿瘤浸润免疫细胞。靶点和途径通过qRT-PCR、免疫组化技术和免疫印迹验证。通过三组实验（模型对照组、抗PD-1组、抗PD-1+MBYF 16.25 g/kg组）验证了MBYF联合抗PD-1的协同效应。MBYF抑制了肿瘤生长和增殖，对心脏、肝脏和肾脏安全。从机制上讲，MBYF通过抑制CCND1、CTNNB1、EGFR以及PI3K-AKT/STAT3/ERK通路的表达降低了肿瘤增殖。此外，MBYF可能通过减少M2-TAM和PMN-MDSC的浸润来提高抗肿瘤免疫（CD4+T细胞、活化CD8+T细胞和NK细胞）。MBYF可能通过下调CCR5-CCLs轴抑制M2-TAM的招募，通过CXCR2-CXCLs轴抑制PMN-MDSC的招募。体内研究证实MBYF增强了抗PD-1疗法的抗肿瘤效应。改良的补肾益气方通过减少M2-TAM和PMN-MDSC的趋化招募来增强肺癌治疗中的抗肿瘤免疫，表明其作为一种辅助疗法增强抗PD-1反应并改善治疗结果的潜力。进一步的研究和临床研究需要验证和拓展这些有希望的发现。版权所有© 2023. Elsevier B.V.出版。

Modified Bushen Yiqi formula (MBYF) has shown efficacy as an herbal combination therapy with anti-PD-1 for lung cancer patients. However, the underlying mechanisms of its antitumor effects in lung cancer remain unclear.This study aims to observe the antitumor effect of MBYF and explore its synergistic mechanism in combination with anti-PD-1 based on the tumor immune microenvironment.The antitumor effect of MBYF was assessed in Lewis Lung Cancer (LLC)-bearing mice by evaluating tumor volume, weight, and histology in five groups (model control, MBYF 8.125 g/kg, MBYF 16.25 g/kg, MBYF 32.50 g/kg, anti-PD-1). Mechanisms were analyzed using pharmacology network and tumor RNA-sequencing. Tumor-infiltrating immune cells were measured by flow cytometry and immunohistochemistry. Targets and pathways were validated through qRT-PCR, immuno-histochemistry, and western blotting. The synergistic effect of MBYF in combination with anti-PD-1 was validated in three groups (model control, anti-PD-1, anti-PD-1+MBYF 16.25 g/kg).MBYF inhibited tumor growth and proliferation and demonstrated safety for the heart, liver, and kidney. Mechanistically, MBYF downregulated tumor proliferation by suppressing the expression of CCND1, CTNNB1, EGFR, and the PI3K-AKT/STAT3/ERK pathway. Furthermore, MBYF may upregulated the antitumor immunity (CD4+T cells, active CD8+ T cells, and NK cells) by reducing the infiltration of M2-TAMs and PMN-MDSCs. MBYF may inhibit the recruitment of M2-TAMs by downregulating the CCR5-CCLs axis and PMN-MDSCs by the CXCR2-CXCLs axis. In vivo study confirmed that MBYF enhanced the antitumor effect of anti-PD-1 therapy.Modified Bushen Yiqi formula enhances antitumor immunity in the treatment of lung cancer by reducing the chemotactic recruitment of M2-TAMs and PMN-MDSCs, suggesting its potential as an adjunct therapy to enhance anti-PD-1 responses and improve treatment outcomes. Further research and clinical studies are needed to validate and expand upon these promising findings.Copyright © 2023. Published by Elsevier B.V.