Melatonin enhances the efficacy of anti-PD-L1 by improving hypoxia in residual tumors after insufficient radiofrequency ablation
10.1016/j.jpha.2024.01.010
- Author:
Ren YANQIAO
1
;
Zhu LICHENG
;
Guo YUSHENG
;
Ma JINQIANG
;
Yang LIAN
;
Zheng CHUANSHENG
;
Dong XIANGJUN
Author Information
1. Department of Radiology,Union Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan,430022,China
- Keywords:
Insufficient radiofrequency ablation;
Melatonin;
Hypoxia;
Immunotherapy
- From:
Journal of Pharmaceutical Analysis
2024;14(8):1176-1188
- CountryChina
- Language:Chinese
-
Abstract:
The hypoxic microenvironment and inflammatory state of residual tumors caused by insufficient radio-frequency ablation(iRFA)are major reasons for rapid tumor progression and pose challenges for immu-notherapy.We retrospectively analyzed the clinical data of patients with hepatocellular carcinoma(HCC)treated with RFA and observed that iRFA was associated with poor survival outcomes and progression-free survival.Using an orthotopic HCC mouse model and a colorectal liver metastasis model,we observed that treatment with melatonin after iRFA reduced tumor growth and metastasis and achieved the best out-comes when combined with anti-programmed death-ligand 1(anti-PD-L1)therapy.In mechanism,melatonin inhibited the expression of epithelial-mesenchymal transitions,hypoxia-inducible factor(HIF)-1 α,and PD-L1 in tumor cells after iRFA.Flow cytometry revealed that melatonin reduced the proportion of myeloid-derived suppressor cells and increased the proportion of CD8+T cells.Transcriptomic analysis revealed an upregulation of immune-activated function-related genes in residual tumors.These findings demonstrated that melatonin can reverse hypoxia and iRFA-induced inflammation,thereby overcoming the immunosuppressive tumor microenvironment(TME)and enhancing the efficacy of immunotherapy.
