Targeted IFNγ induction by a genetically engineered Salmonella typhimurium is the key to the liver metastasis inhibition in a mouse model of pancreatic neuroendocrine tumor

作者：Zhan Hua, Shan Wu, Yulian Zhang, Xiuhong Wang, Ju Cui, Yunxuan Li, Chengcheng Yang, Min Zhai, Bo Deng, Bin Yu, Jian‐Dong Huang, Zai Wang, Jianjun Zhou · 发表于：Frontiers in Medicine · 年份：2023 · DOI：10.3389/fmed.2023.1284120 · 被引用次数：2 · 研究领域：Cancer Research and Treatments、Neuroendocrine Tumor Research Advances、Cancer, Stress, Anesthesia, and Immune Response

Background: Liver metastasis is one of the primary causes of death for the patients with pancreatic neuroendocrine tumors (PNETs). However, no curative therapy has been developed so far. Methods: YB1 was evaluated on a non-functional INR1G9 liver metastasis model. Differential inflammatory factors were screened by Cytometric Bead Array. Antibody depletion assay and liver-targeted AAV2/8 expression vector were used for functional evaluation of the differential inflammatory factors. Results: We demonstrated that YB1 showed significant anti-tumor efficacy as a monotherapy. Since YB1 cannot infect INR1G9 cells, its anti-tumor effect was possibly due to the modulation of the tumor immune microenvironment. Two inflammatory factors IFNγ and CCL2 were elevated in the liver after YB1 administration, but only IFNγ was found to be responsible for the anti-tumor effect. Liver-targeted expression of IFNγ caused the activation of macrophages and NK cells, and reproduced the therapeutic effect of YB1 on liver metastasis. Conclusion: We demonstrated that YB1 may exhibit anti-tumor effect mainly based on IFNγ induction. Targeted IFNγ therapy can replace YB1 for treating liver metastasis of PNETs.