Digestive diseases and sciences · 2025
Aflatoxin B1 Promotes M2-like Macrophage Polarization via IL-6 Expression in Hepatocellular Carcinoma.
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Niu Jingze, Wu Wenda, Zhang Huayue, Li Zelin, Meng Xiaojie, Xu Baocai
Аннотация
BACKGROUND: The development of liver cancer in China is mainly caused by HBV, HCV infection, and exposure to aflatoxin. Especially in warm and humid southern regions, aflatoxin pollution poses a threat to health, emphasizing the urgency of research on related liver cancer.
METHODS: Firstly, through in vivo experiments, the important role of AFB1 in mediating changes in the immune microenvironment of liver cancer has been preliminarily validated. In addition, statistical and mIHC analysis were conducted on clinical specimens collected from patients exposed and non-exposed to aflatoxin. Transcriptome sequencing technology enabled us to further explore the specific molecular mechanisms underlying the occurrence of HCC caused by AFB1 exposure. Finally, the synergistic effect of targeting IL-6 on PD1 therapy was validated through an in vivo animal tumor model.
RESULTS: We found that AFB1 indirectly influences M2-like macrophage polarization by upregulating IL-6 expression in tumor cells through the NF-κB signaling pathway. To address this challenge, we evaluated the efficacy of targeting IL-6 in combination with PD1 antibody therapy in a subcutaneous tumor model. Our results demonstrate that the combination treatment significantly reduces tumor growth, decreases the number of M2-like macrophages, and enhances CD8 + T cell infiltration compared to monotherapy with PD1 antibody alone.
CONCLUSIONS: Overall, our study highlights the potential of targeting IL-6 as a therapeutic strategy and suggests avenues for further research and clinical studies to validate and translate these findings into clinical applications, ultimately leading to improved outcomes for patients with AFB1-associated hepatocellular carcinoma.
METHODS: Firstly, through in vivo experiments, the important role of AFB1 in mediating changes in the immune microenvironment of liver cancer has been preliminarily validated. In addition, statistical and mIHC analysis were conducted on clinical specimens collected from patients exposed and non-exposed to aflatoxin. Transcriptome sequencing technology enabled us to further explore the specific molecular mechanisms underlying the occurrence of HCC caused by AFB1 exposure. Finally, the synergistic effect of targeting IL-6 on PD1 therapy was validated through an in vivo animal tumor model.
RESULTS: We found that AFB1 indirectly influences M2-like macrophage polarization by upregulating IL-6 expression in tumor cells through the NF-κB signaling pathway. To address this challenge, we evaluated the efficacy of targeting IL-6 in combination with PD1 antibody therapy in a subcutaneous tumor model. Our results demonstrate that the combination treatment significantly reduces tumor growth, decreases the number of M2-like macrophages, and enhances CD8 + T cell infiltration compared to monotherapy with PD1 antibody alone.
CONCLUSIONS: Overall, our study highlights the potential of targeting IL-6 as a therapeutic strategy and suggests avenues for further research and clinical studies to validate and translate these findings into clinical applications, ultimately leading to improved outcomes for patients with AFB1-associated hepatocellular carcinoma.