Na Se Won, Yi Jin-Mu, Yeo Heerim, Park Sang-Min, Jeong Mibae, Chun Jaemoo, Jeong Mi-Kyung
KM Convergence Research Division, Korea Institute of Oriental Medicine, Daejeon 34054, Republic of Korea.
College of Pharmacy, Chungnam National University, Daejeon 34134, Republic of Korea.
Life (Basel). 2024 Sep 30;14(10):1246. doi: 10.3390/life14101246.
Bojungikki-Tang (BJIKT) is traditionally used to enhance digestive function and immunity. It has gained attention as a supplement to chemotherapy or targeted therapy owing to its immune-boosting properties. This study aimed to evaluate the synergistic anti-tumor effects of BJIKT in combination with pembrolizumab in a preclinical model. MHC I/II double knockout NSG mice were humanized with peripheral blood mononuclear cells (PBMCs) and injected subcutaneously with H460 lung tumor cells to establish a humanized tumor model. Both agents were administered to evaluate their impact on tumor growth and immune cell behavior. Immunohistochemistry showed decreased exhaustion markers in CD8(+) and CD4(+) T cells within the tumor, indicating enhanced T cell activity. Additionally, RNA sequencing, transcriptome analysis, and quantitative PCR analysis were performed on tumor tissues to investigate the molecular mechanisms underlying the observed effects. The results confirmed that BJIKT improved T cell function and tumor necrosis factor signaling while suppressing transforming growth factor-β signaling. This modulation led to cell cycle arrest and apoptosis. These findings demonstrate that BJIKT, when combined with pembrolizumab, produces significant anti-tumor effects by altering immune pathways and enhancing the anti-tumor immune response. This study provides valuable insights into the role of BJIKT in the tumor microenvironment and its potential to improve therapeutic outcomes.
补中益气汤传统上用于增强消化功能和免疫力。由于其增强免疫力的特性，它作为化疗或靶向治疗的补充剂而受到关注。本研究旨在评估在临床前模型中补中益气汤与帕博利珠单抗联合使用的协同抗肿瘤作用。将MHC I/II双敲除NSG小鼠用人外周血单个核细胞（PBMC）进行人源化处理，并皮下注射H460肺肿瘤细胞以建立人源化肿瘤模型。给予两种药物以评估它们对肿瘤生长和免疫细胞行为的影响。免疫组织化学显示肿瘤内CD8(+)和CD4(+) T细胞中的耗竭标志物减少，表明T细胞活性增强。此外，对肿瘤组织进行RNA测序、转录组分析和定量PCR分析，以研究观察到的效应背后的分子机制。结果证实，补中益气汤改善了T细胞功能和肿瘤坏死因子信号传导，同时抑制了转化生长因子-β信号传导。这种调节导致细胞周期停滞和细胞凋亡。这些发现表明，补中益气汤与帕博利珠单抗联合使用时，通过改变免疫途径和增强抗肿瘤免疫反应产生显著的抗肿瘤作用。本研究为补中益气汤在肿瘤微环境中的作用及其改善治疗效果的潜力提供了有价值的见解。
