Objective:Although the role of circular RNAs(circRNAs)in tumor progression and immune regulation is well-known,the specific circ RNA molecules that mediate immune responses after radiotherapy(RT)and the underlying mec...Objective:Although the role of circular RNAs(circRNAs)in tumor progression and immune regulation is well-known,the specific circ RNA molecules that mediate immune responses after radiotherapy(RT)and the underlying mechanisms have not been identified.Methods:Cytometry with time-of-flight(CyTOF)was used to analyze blood samples from patients with liver cancer exhibiting abscopal effects(AEs)after stereotactic body radiotherapy(SBRT)to quantify the number of dendritic cells(DCs)and CD8+T cells and interferon-beta(IFN-β)level.circTMEM56 and IFN-βlevels were measured in 76 patients with liver cancer using q PCR and ELISA.Immunohistochemistry validated circTMEM56 and CD141 staining in tissues.The interaction between circTMEM56,miR-136-5p,and STING,as well as the impact on anti-tumor immunity,was verified using circTMEM56-specific probes,dual-luciferase activity assays,proteomics analysis,and western blot analysis.Results:The role of circTMEM56 in enhancing anti-tumor immunity and response to RT in hepatocellular carcinoma(HCC)was determined.Higher circTMEM56 levels were linked to an improved RT response and better clinical outcomes in patients with HCC.circTMEM56 enhanced cGAS-STING signaling,increased the number of tumor-infiltrating CD8+T cells,and elevated the serum IFN-βlevels.Moreover,circTMEM56 administration significantly boosted the response to RT in tumors with low circTMEM56 expression.Conclusions:High circTMEM56 expression in HCC modulates the distant effects of HCC RT by activating the cGAS-STING pathway to reshape the tumor microenvironment.This study provides a new approach to improve RT efficacy for HCC.展开更多
基金funded by the National Key Research and Development Program of China(Grant No.2023YFC3402700)Shanghai Municipal Natural Science Foundation(Grant No.22ZR1411200)+2 种基金China Postdoctoral Science FundGeneral Fund(Grant No.2022M720779)Research Fund of Zhongshan Hospital Affiliated to Shanghai Fudan University for Young Scientists(Grant No.2023ZSQN26)National Natural Science Foundation of China(Grant Nos.82403999 and 82073479)。
文摘Objective:Although the role of circular RNAs(circRNAs)in tumor progression and immune regulation is well-known,the specific circ RNA molecules that mediate immune responses after radiotherapy(RT)and the underlying mechanisms have not been identified.Methods:Cytometry with time-of-flight(CyTOF)was used to analyze blood samples from patients with liver cancer exhibiting abscopal effects(AEs)after stereotactic body radiotherapy(SBRT)to quantify the number of dendritic cells(DCs)and CD8+T cells and interferon-beta(IFN-β)level.circTMEM56 and IFN-βlevels were measured in 76 patients with liver cancer using q PCR and ELISA.Immunohistochemistry validated circTMEM56 and CD141 staining in tissues.The interaction between circTMEM56,miR-136-5p,and STING,as well as the impact on anti-tumor immunity,was verified using circTMEM56-specific probes,dual-luciferase activity assays,proteomics analysis,and western blot analysis.Results:The role of circTMEM56 in enhancing anti-tumor immunity and response to RT in hepatocellular carcinoma(HCC)was determined.Higher circTMEM56 levels were linked to an improved RT response and better clinical outcomes in patients with HCC.circTMEM56 enhanced cGAS-STING signaling,increased the number of tumor-infiltrating CD8+T cells,and elevated the serum IFN-βlevels.Moreover,circTMEM56 administration significantly boosted the response to RT in tumors with low circTMEM56 expression.Conclusions:High circTMEM56 expression in HCC modulates the distant effects of HCC RT by activating the cGAS-STING pathway to reshape the tumor microenvironment.This study provides a new approach to improve RT efficacy for HCC.
