Background:Aberrant expression of transcription factors(TFs)is a key mechanism mediating tumor immune escape and therapeutic resistance.The involvement of E26 transformation-specific(ETS)family of TFs in immune regula...Background:Aberrant expression of transcription factors(TFs)is a key mechanism mediating tumor immune escape and therapeutic resistance.The involvement of E26 transformation-specific(ETS)family of TFs in immune regulation is not fully understood.The study aimed to elucidate the function of E-twenty-six variant 4(ETV4)in tumor immune evasion and its potential as a predictive biomarker for immunotherapy in melanoma.Methods:The expression patterns of ETS family TFs were analyzed in melanoma and hepatocellular carcinoma(HCC).Single-cell RNA sequencing(scRNA-seq)was used to dissect the cellular expression and function of ETV4 in the tumor microenvironment.Functional studies and murine models were employed to investigate the role of ETV4 in T cell-mediated tumor killing and tumor growth.The correlation between ETV4 expression level and patient responsiveness to programmed cell death protein 1(PD-1)blockade therapy was evaluated.Results:TFs in the ETS family were found to effectively stratify melanoma and HCC patients into prognostic subgroups.In melanoma,the polyoma enhancer activator 3(PEA3)subfamily,particularly ETV4 and ETV5,showed a negative correlation with immune infiltration.scRNA-seq analysis showed that ETV4 is preferentially expressed in melanoma cells and involves in mediating tumor-immunocyte interactions.Functional studies demonstrated that ETV4 impairs T cell-mediated tumor killing by transcriptionally upregulating programmed death-ligand 1(PD-L1).In immunocompetent murine models,ETV4 downregulation significantly suppressed tumor growth.Furthermore,high ETV4 expression correlated with poor responses to anti-PD-1 therapy.Conclusion:Our findings identify ETV4 as a key transcriptional regulator of immune evasion in melanoma by controlling PD-L1 expression.ETV4 may act as a predictive biomarker for immunotherapy outcomes.展开更多
背景精准评估癌症患者的疲劳程度,有利于准确识别癌症患者的疲劳严重程度以及针对性地制定干预措施。目前国内外评估癌症患者的疲劳工具种类繁多,但缺乏量表测量学特性的系统整合,给合理规范地选择评估工具带来了困难。目的评估癌症患...背景精准评估癌症患者的疲劳程度,有利于准确识别癌症患者的疲劳严重程度以及针对性地制定干预措施。目前国内外评估癌症患者的疲劳工具种类繁多,但缺乏量表测量学特性的系统整合,给合理规范地选择评估工具带来了困难。目的评估癌症患者疲劳测量工具的方法学和测量特性。方法检索中国知网(CNKI)、万方数据知识服务平台(Wanfang Data)、维普网(VIP)、中国生物医学文献服务系统(SinoMed)、PubMed、Embase、Cochrane Library、Web of Science中关于癌症患者疲劳评估工具的研究,检索时限为建库至2024-05-31。由两位研究者独立筛选、交叉核对后,依据健康测量工具选择共识标准(COSMIN)对纳入的研究进行评价,并生成推荐意见。结果共纳入22篇文献,包括:儿童多维疲劳量表(PedsQLTMMFS)、中文版PedsQLTMMFS、癌症治疗功能评估疲乏量表(FACT)、中文版FACT(FACT-F)、多维度疲乏量表(MFI-20)、中文版MFI-20、癌因性疲乏量表、癌因性疲乏综合筛查量表、癌因性疲乏自评量表、多维疲劳症状量表(MFSI)、中文版MFSI-简表(MFSI-SF)、疲乏症状量表(FSI)、每日疲劳癌量表(DFCS)、儿童疲劳量表、中文版儿童疲劳量表(CF-C)、癌症疲乏量表(CFS)、中文版CFS(CFS-C)、癌症疲劳量表(CF)、简易疲乏量表(BFI)、癌症相关疲劳问卷、Piper疲乏修订量表(PFS-R)、Schwartz癌症疲乏量表(SCFS)共计22种癌症患者相关疲劳评估工具。所有评估工具内容效度为不确定,证据质量为中等或以下,其中19个量表为B级推荐,3个量表为C级推荐。结论目前推荐MFSI用于癌症患者疲劳的评估(推荐等级为B级),但其方法学质量与测量学特性仍有待提高。展开更多
基金funded by the National Natural Science Foundation of China(Grant Nos.82204517 to T.Z.and 82404756 to J.Z.)the Science and Technology Program in Medicine and Health of Zhejiang Province(Grant No.2023KY726 to T.Z.).
文摘Background:Aberrant expression of transcription factors(TFs)is a key mechanism mediating tumor immune escape and therapeutic resistance.The involvement of E26 transformation-specific(ETS)family of TFs in immune regulation is not fully understood.The study aimed to elucidate the function of E-twenty-six variant 4(ETV4)in tumor immune evasion and its potential as a predictive biomarker for immunotherapy in melanoma.Methods:The expression patterns of ETS family TFs were analyzed in melanoma and hepatocellular carcinoma(HCC).Single-cell RNA sequencing(scRNA-seq)was used to dissect the cellular expression and function of ETV4 in the tumor microenvironment.Functional studies and murine models were employed to investigate the role of ETV4 in T cell-mediated tumor killing and tumor growth.The correlation between ETV4 expression level and patient responsiveness to programmed cell death protein 1(PD-1)blockade therapy was evaluated.Results:TFs in the ETS family were found to effectively stratify melanoma and HCC patients into prognostic subgroups.In melanoma,the polyoma enhancer activator 3(PEA3)subfamily,particularly ETV4 and ETV5,showed a negative correlation with immune infiltration.scRNA-seq analysis showed that ETV4 is preferentially expressed in melanoma cells and involves in mediating tumor-immunocyte interactions.Functional studies demonstrated that ETV4 impairs T cell-mediated tumor killing by transcriptionally upregulating programmed death-ligand 1(PD-L1).In immunocompetent murine models,ETV4 downregulation significantly suppressed tumor growth.Furthermore,high ETV4 expression correlated with poor responses to anti-PD-1 therapy.Conclusion:Our findings identify ETV4 as a key transcriptional regulator of immune evasion in melanoma by controlling PD-L1 expression.ETV4 may act as a predictive biomarker for immunotherapy outcomes.
文摘背景精准评估癌症患者的疲劳程度,有利于准确识别癌症患者的疲劳严重程度以及针对性地制定干预措施。目前国内外评估癌症患者的疲劳工具种类繁多,但缺乏量表测量学特性的系统整合,给合理规范地选择评估工具带来了困难。目的评估癌症患者疲劳测量工具的方法学和测量特性。方法检索中国知网(CNKI)、万方数据知识服务平台(Wanfang Data)、维普网(VIP)、中国生物医学文献服务系统(SinoMed)、PubMed、Embase、Cochrane Library、Web of Science中关于癌症患者疲劳评估工具的研究,检索时限为建库至2024-05-31。由两位研究者独立筛选、交叉核对后,依据健康测量工具选择共识标准(COSMIN)对纳入的研究进行评价,并生成推荐意见。结果共纳入22篇文献,包括:儿童多维疲劳量表(PedsQLTMMFS)、中文版PedsQLTMMFS、癌症治疗功能评估疲乏量表(FACT)、中文版FACT(FACT-F)、多维度疲乏量表(MFI-20)、中文版MFI-20、癌因性疲乏量表、癌因性疲乏综合筛查量表、癌因性疲乏自评量表、多维疲劳症状量表(MFSI)、中文版MFSI-简表(MFSI-SF)、疲乏症状量表(FSI)、每日疲劳癌量表(DFCS)、儿童疲劳量表、中文版儿童疲劳量表(CF-C)、癌症疲乏量表(CFS)、中文版CFS(CFS-C)、癌症疲劳量表(CF)、简易疲乏量表(BFI)、癌症相关疲劳问卷、Piper疲乏修订量表(PFS-R)、Schwartz癌症疲乏量表(SCFS)共计22种癌症患者相关疲劳评估工具。所有评估工具内容效度为不确定,证据质量为中等或以下,其中19个量表为B级推荐,3个量表为C级推荐。结论目前推荐MFSI用于癌症患者疲劳的评估(推荐等级为B级),但其方法学质量与测量学特性仍有待提高。
