头颈部鳞状细胞癌是起源于头颈解剖部位黏膜上皮的恶性肿瘤,目前较为明确的危险因素包括烟草、酒精、槟榔、电离辐射等。头颈部鳞状细胞癌患者可出现口颌颈部肿胀、牙齿松动脱落、咀嚼吞咽困难、皮肤感觉异常、鼻阻塞等多种临床症状,5...头颈部鳞状细胞癌是起源于头颈解剖部位黏膜上皮的恶性肿瘤,目前较为明确的危险因素包括烟草、酒精、槟榔、电离辐射等。头颈部鳞状细胞癌患者可出现口颌颈部肿胀、牙齿松动脱落、咀嚼吞咽困难、皮肤感觉异常、鼻阻塞等多种临床症状,5年生存率仅为50%。近年来随着免疫学发展,免疫抑制性肿瘤微环境逐渐成为研究热点,基于细胞程序性死亡受体1(programmed cell death 1,PD-1)/细胞程序性死亡配体1(programmed cell death 1 ligand 1,PD-L1)抑制剂的免疫治疗方案已取得显著的临床效果。展开更多
Background:Exercise exerts tumor-suppressive effects across multiple malignancies,partly through exerkines—exercise-induced secreted factors with immunomodulatory and metabolic functions.However,the prognostic releva...Background:Exercise exerts tumor-suppressive effects across multiple malignancies,partly through exerkines—exercise-induced secreted factors with immunomodulatory and metabolic functions.However,the prognostic relevance of exerkines across cancer types remains unclear,and the molecular determinants of exercise responsiveness are poorly defined.Methods:We systematically profiled 183 curated exerkine-related genes across 33 cancer types from The Cancer Genome Atlas(TCGA)using non-negative matrix factorization(NMF)to define molecular subtypes.Prognostic significance was evaluated via Kaplan-Meier analysis.For five cancers with consistent survival divergence(LGG,KIRC,LUAD,PAAD,ACC),we developed an Exerkine Prognostic Index(EPI)using LASSO Cox regression and validated its predictive performance through time-dependent ROC analysis.Immune cell infiltration(CIBERSORT),stromal/immune scores(ESTIMATE),and immune checkpoint expression were assessed to characterize immune landscape differences between EPI subgroups.Results:Exerkine-based NMF clustering identified prognostically distinct subtypes in 25 cancers.The EPI robustly stratified patients into high-and low-risk groups with significant differences in overall survival(p<0.001).High-EPI subgroups were associated with elevated infiltration of immunosuppressive cells(e.g.,Tregs,M0 macrophages),altered immune/stromal scores,and differential expression of immune checkpoints such as PD-L1 and CTLA4 in a cancer-type-specific manner.Discussion:Our findings reveal that exerkine expression patterns capture biologically and clinically relevant heterogeneity across cancers.The EPI provides a robust molecular tool to stratify patients by prognosis and immune contexture,offering insights into differential exercise responsiveness.Conclusions:Exerkines represent promising biomarkers for risk stratification and precision-guided exercise interventions in oncology.展开更多
热休克蛋白70羧基末端相互作用蛋白(C-terminal of Hsp70-interacting protein,CHIP)是一种属于U-box家族的泛素连接酶和共伴侣,在维持细胞稳态中发挥关键作用。CHIP通过调节蛋白质的折叠-重折叠过程,将肿瘤关键蛋白转变至蛋白酶体或溶...热休克蛋白70羧基末端相互作用蛋白(C-terminal of Hsp70-interacting protein,CHIP)是一种属于U-box家族的泛素连接酶和共伴侣,在维持细胞稳态中发挥关键作用。CHIP通过调节蛋白质的折叠-重折叠过程,将肿瘤关键蛋白转变至蛋白酶体或溶酶体降解途径。它可通过N端四重螺旋重复序列(tetratricopeptide repeat,TPR)域与分子伴侣[如热休克蛋白70(HSP70)和热休克蛋白90(HSP90)相互作用,并通过C端U-box域促进泛素转移至底物蛋白,从而执行泛素化降解。近年来,研究发现E3泛素连接酶(STUB1)基因(STIP1同源性和含U-box蛋白1)编码的CHIP蛋白在多种恶性肿瘤中既可发挥肿瘤抑制功能,也可能在特定条件下促进肿瘤进展,被视为一种“双面间谍”。此外,STUB1/CHIP在多种免疫细胞的分化、成熟及免疫检查点通路中均具重要调控作用。现系统综述STUB1/CHIP在癌症进展与肿瘤免疫中的生物学功能、临床意义及潜在的治疗价值,探讨其在精准医疗和免疫治疗领域的研究前景。展开更多
近年来,肿瘤浸润性B淋巴细胞(tumor-infiltrating B lymphocytes,TIL-B)在肿瘤的发生和发展中扮演着复杂且重要的角色。这些细胞通过多种机制参与抗肿瘤免疫反应,但同时也可能在特定刺激下获得抑制功能,转化为调节性B细胞(regulatory B ...近年来,肿瘤浸润性B淋巴细胞(tumor-infiltrating B lymphocytes,TIL-B)在肿瘤的发生和发展中扮演着复杂且重要的角色。这些细胞通过多种机制参与抗肿瘤免疫反应,但同时也可能在特定刺激下获得抑制功能,转化为调节性B细胞(regulatory B cells,Bregs),进而抑制肿瘤免疫应答,促进肿瘤的进展。越来越多的证据表明,TIL-B不仅是抗肿瘤免疫治疗中有效的靶标,而且在疾病预后方面也具有重要作用。本文综述了TIL-B研究现状,总结了其在肿瘤免疫中的作用机制,分析了当前的治疗策略和预后评估方法,并对未来的研究方向进行了展望。通过深入理解TIL-B的复杂性,可以为开发新的肿瘤治疗策略提供理论基础和潜在靶点。展开更多
文摘头颈部鳞状细胞癌是起源于头颈解剖部位黏膜上皮的恶性肿瘤,目前较为明确的危险因素包括烟草、酒精、槟榔、电离辐射等。头颈部鳞状细胞癌患者可出现口颌颈部肿胀、牙齿松动脱落、咀嚼吞咽困难、皮肤感觉异常、鼻阻塞等多种临床症状,5年生存率仅为50%。近年来随着免疫学发展,免疫抑制性肿瘤微环境逐渐成为研究热点,基于细胞程序性死亡受体1(programmed cell death 1,PD-1)/细胞程序性死亡配体1(programmed cell death 1 ligand 1,PD-L1)抑制剂的免疫治疗方案已取得显著的临床效果。
基金supported by Beijing Sport University Graduate Innovation Programme(2024013).
文摘Background:Exercise exerts tumor-suppressive effects across multiple malignancies,partly through exerkines—exercise-induced secreted factors with immunomodulatory and metabolic functions.However,the prognostic relevance of exerkines across cancer types remains unclear,and the molecular determinants of exercise responsiveness are poorly defined.Methods:We systematically profiled 183 curated exerkine-related genes across 33 cancer types from The Cancer Genome Atlas(TCGA)using non-negative matrix factorization(NMF)to define molecular subtypes.Prognostic significance was evaluated via Kaplan-Meier analysis.For five cancers with consistent survival divergence(LGG,KIRC,LUAD,PAAD,ACC),we developed an Exerkine Prognostic Index(EPI)using LASSO Cox regression and validated its predictive performance through time-dependent ROC analysis.Immune cell infiltration(CIBERSORT),stromal/immune scores(ESTIMATE),and immune checkpoint expression were assessed to characterize immune landscape differences between EPI subgroups.Results:Exerkine-based NMF clustering identified prognostically distinct subtypes in 25 cancers.The EPI robustly stratified patients into high-and low-risk groups with significant differences in overall survival(p<0.001).High-EPI subgroups were associated with elevated infiltration of immunosuppressive cells(e.g.,Tregs,M0 macrophages),altered immune/stromal scores,and differential expression of immune checkpoints such as PD-L1 and CTLA4 in a cancer-type-specific manner.Discussion:Our findings reveal that exerkine expression patterns capture biologically and clinically relevant heterogeneity across cancers.The EPI provides a robust molecular tool to stratify patients by prognosis and immune contexture,offering insights into differential exercise responsiveness.Conclusions:Exerkines represent promising biomarkers for risk stratification and precision-guided exercise interventions in oncology.
文摘热休克蛋白70羧基末端相互作用蛋白(C-terminal of Hsp70-interacting protein,CHIP)是一种属于U-box家族的泛素连接酶和共伴侣,在维持细胞稳态中发挥关键作用。CHIP通过调节蛋白质的折叠-重折叠过程,将肿瘤关键蛋白转变至蛋白酶体或溶酶体降解途径。它可通过N端四重螺旋重复序列(tetratricopeptide repeat,TPR)域与分子伴侣[如热休克蛋白70(HSP70)和热休克蛋白90(HSP90)相互作用,并通过C端U-box域促进泛素转移至底物蛋白,从而执行泛素化降解。近年来,研究发现E3泛素连接酶(STUB1)基因(STIP1同源性和含U-box蛋白1)编码的CHIP蛋白在多种恶性肿瘤中既可发挥肿瘤抑制功能,也可能在特定条件下促进肿瘤进展,被视为一种“双面间谍”。此外,STUB1/CHIP在多种免疫细胞的分化、成熟及免疫检查点通路中均具重要调控作用。现系统综述STUB1/CHIP在癌症进展与肿瘤免疫中的生物学功能、临床意义及潜在的治疗价值,探讨其在精准医疗和免疫治疗领域的研究前景。
文摘近年来,肿瘤浸润性B淋巴细胞(tumor-infiltrating B lymphocytes,TIL-B)在肿瘤的发生和发展中扮演着复杂且重要的角色。这些细胞通过多种机制参与抗肿瘤免疫反应,但同时也可能在特定刺激下获得抑制功能,转化为调节性B细胞(regulatory B cells,Bregs),进而抑制肿瘤免疫应答,促进肿瘤的进展。越来越多的证据表明,TIL-B不仅是抗肿瘤免疫治疗中有效的靶标,而且在疾病预后方面也具有重要作用。本文综述了TIL-B研究现状,总结了其在肿瘤免疫中的作用机制,分析了当前的治疗策略和预后评估方法,并对未来的研究方向进行了展望。通过深入理解TIL-B的复杂性,可以为开发新的肿瘤治疗策略提供理论基础和潜在靶点。
