转化生长因子-β（TGF-β）与免疫细胞：肿瘤微环境和进展中的重要调节轴。
TGF-beta and immune cells: an important regulatory axis in the tumor microenvironment and progression.
机构信息
Laboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20876, USA.
出版信息
Trends Immunol. 2010 Jun;31(6):220-7. doi: 10.1016/j.it.2010.04.002. Epub 2010 Jun 1.
Abstract
Transforming growth factor beta (TGF-beta) plays an important role in tumor initiation and progression, functioning as both a suppressor and a promoter. The mechanisms underlying this dual role of TGF-beta remain unclear. TGF-beta exerts systemic immune suppression and inhibits host immunosurveillance. Neutralizing TGF-beta enhances CD8+ T-cell- and NK-cell-mediated anti-tumor immune responses. It also increases neutrophil-attracting chemokines resulting in recruitment and activation of neutrophils with an antitumor phenotype. In addition to its systemic effects, TGF-beta regulates infiltration of inflammatory/immune cells and cancer-associated fibroblasts in the tumor microenvironment causing direct changes in tumor cells. Understanding TGF-beta regulation at the interface of tumor and host immunity should provide insights into developing effective TGF-beta antagonists and biomarkers for patient selection and efficacy of TGF-beta antagonist treatment.
摘要
转化生长因子β（TGF-β）在肿瘤的发生和发展中起着重要作用，既是抑制因子又是促进因子。TGF-β这种双重作用的机制尚不清楚。TGF-β发挥全身免疫抑制作用，抑制宿主免疫监视。中和 TGF-β可增强 CD8+T 细胞和 NK 细胞介导的抗肿瘤免疫反应。它还增加了吸引中性粒细胞的趋化因子，导致具有抗肿瘤表型的中性粒细胞募集和激活。除了全身作用外，TGF-β还调节肿瘤微环境中炎症/免疫细胞和癌相关成纤维细胞的浸润，导致肿瘤细胞的直接变化。了解肿瘤与宿主免疫界面的 TGF-β调节，应可为开发有效的 TGF-β拮抗剂和生物标志物，用于患者选择和 TGF-β拮抗剂治疗的疗效提供思路。
相似文献
1
TGF-beta and immune cells: an important regulatory axis in the tumor microenvironment and progression.转化生长因子-β（TGF-β）与免疫细胞：肿瘤微环境和进展中的重要调节轴。
Trends Immunol. 2010 Jun;31(6):220-7. doi: 10.1016/j.it.2010.04.002. Epub 2010 Jun 1.
2
Human tumour immune evasion via TGF-β blocks NK cell activation but not survival allowing therapeutic restoration of anti-tumour activity.通过 TGF-β 阻断 NK 细胞激活但不影响存活，实现人类肿瘤免疫逃逸，从而允许通过治疗恢复抗肿瘤活性。
PLoS One. 2011;6(9):e22842. doi: 10.1371/journal.pone.0022842. Epub 2011 Sep 6.
3
TGF-β regulated leukemia cell susceptibility against NK targeting through the down-regulation of the CD48 expression.TGF-β 通过下调 CD48 表达调节白血病细胞对 NK 靶向的敏感性。
Immunobiology. 2019 Sep;224(5):649-658. doi: 10.1016/j.imbio.2019.07.002. Epub 2019 Aug 9.
4
TGFbeta, a potent regulator of tumor microenvironment and host immune response, implication for therapy.TGFbeta，一种有效的肿瘤微环境和宿主免疫反应调节剂，对治疗有启示作用。
Curr Mol Med. 2010 Jun;10(4):374-80. doi: 10.2174/156652410791317039.
5
Platelet-derived transforming growth factor-beta down-regulates NKG2D thereby inhibiting natural killer cell antitumor reactivity.血小板衍生的转化生长因子-β下调NKG2D，从而抑制自然杀伤细胞的抗肿瘤反应性。
Cancer Res. 2009 Oct 1;69(19):7775-83. doi: 10.1158/0008-5472.CAN-09-2123. Epub 2009 Sep 8.
6
TGF-β-inducible microRNA-183 silences tumor-associated natural killer cells.TGF-β 诱导的 microRNA-183 沉默肿瘤相关自然杀伤细胞。
Proc Natl Acad Sci U S A. 2014 Mar 18;111(11):4203-8. doi: 10.1073/pnas.1319269111. Epub 2014 Feb 28.
7
TGF-β Family Signaling in Tumor Suppression and Cancer Progression.TGF-β 家族信号在肿瘤抑制和癌症进展中的作用。
Cold Spring Harb Perspect Biol. 2017 Dec 1;9(12):a022277. doi: 10.1101/cshperspect.a022277.
8
Transforming growth factor-beta: recent advances on its role in immune tolerance.转化生长因子-β：其在免疫耐受中作用的最新进展
Curr Rheumatol Rep. 2006 Apr;8(2):138-44. doi: 10.1007/s11926-006-0054-y.
9
Improving function of cytotoxic T-lymphocytes by transforming growth factor-β inhibitor in oral squamous cell carcinoma.转化生长因子-β抑制剂改善口腔鳞状细胞癌细胞毒性 T 淋巴细胞的功能。
Cancer Sci. 2021 Oct;112(10):4037-4049. doi: 10.1111/cas.15081. Epub 2021 Aug 2.
10
TGF-beta signaling, tumor microenvironment and tumor progression: the butterfly effect.TGF-β 信号转导、肿瘤微环境与肿瘤演进：蝴蝶效应。
Front Biosci (Landmark Ed). 2010 Jan 1;15(1):180-94. doi: 10.2741/3614.
引用本文的文献
1
Targeting archetypes of viral-driven cancers with immunotherapy: a perspective on immunogenicity within the tumor microenvironment.用免疫疗法靶向病毒驱动癌症的原型：关于肿瘤微环境中免疫原性的观点
Front Immunol. 2025 Aug 29;16:1631258. doi: 10.3389/fimmu.2025.1631258. eCollection 2025.
2
Immune evasion in cancer: mechanisms and cutting-edge therapeutic approaches.癌症中的免疫逃逸：机制与前沿治疗方法。
Signal Transduct Target Ther. 2025 Jul 31;10(1):227. doi: 10.1038/s41392-025-02280-1.
3
Dual-Faced Role of GDF6 in Cancer: Mechanistic Insights into Its Context-Dependent Regulation of Metastasis and Immune Evasion Across Human Malignancies.生长分化因子6（GDF6）在癌症中的双面作用：对其在人类恶性肿瘤中转移和免疫逃逸的上下文依赖性调控的机制洞察
Curr Issues Mol Biol. 2025 Apr 2;47(4):249. doi: 10.3390/cimb47040249.
4
UNC93B1: a novel immune-related prognostic biomarker in breast cancer.UNC93B1：一种新型的乳腺癌免疫相关预后生物标志物。
Discov Oncol. 2025 Jul 17;16(1):1352. doi: 10.1007/s12672-025-03124-8.
5
The Role of Fibroblasts in Melanoma Development: From Tumor Microenvironment Remodeling to Pre-Metastatic Niche Formation.成纤维细胞在黑色素瘤发展中的作用：从肿瘤微环境重塑到前转移生态位形成
Int J Mol Sci. 2025 Jun 26;26(13):6132. doi: 10.3390/ijms26136132.
6
The prognostic significance of the NMD core factor UPF1 in low-grade glioma.NMD核心因子UPF1在低级别胶质瘤中的预后意义
Sci Rep. 2025 Jul 1;15(1):20574. doi: 10.1038/s41598-025-05711-9.
7
Revisiting Treatment Strategies: Addressing Epithelial-to-Mesenchymal Transition-Induced Resistance in Hepatocellular Carcinoma.重新审视治疗策略：应对肝细胞癌中上皮-间质转化诱导的耐药性
BME Front. 2025 Jun 24;6:0144. doi: 10.34133/bmef.0144. eCollection 2025.
8
PET/CT imaging of esophageal cancer targeting tumor cell specific αvβ6-integrin expression.针对肿瘤细胞特异性αvβ6整合素表达的食管癌PET/CT成像。
Eur J Nucl Med Mol Imaging. 2025 Jun 20. doi: 10.1007/s00259-025-07408-7.
9
Proteomic and metabolomic profiling of extracellular vesicles produced by human gut archaea.人类肠道古菌产生的细胞外囊泡的蛋白质组学和代谢组学分析
Nat Commun. 2025 Jun 3;16(1):5094. doi: 10.1038/s41467-025-60271-w.
10
Medicinal Chemistry Strategies in Targeting TGF-βR1 Kinase Domain: Unveiling Insights into Inhibitor Structure-Activity Relationship (SAR).靶向转化生长因子-β受体1激酶结构域的药物化学策略：揭示抑制剂构效关系（SAR）的见解
Pharmaceuticals (Basel). 2025 May 13;18(5):716. doi: 10.3390/ph18050716.
本文引用的文献
1
Synergistic enhancement of CD8+ T cell-mediated tumor vaccine efficacy by an anti-transforming growth factor-beta monoclonal antibody.抗转化生长因子-β单克隆抗体协同增强CD8 + T细胞介导的肿瘤疫苗疗效
Clin Cancer Res. 2009 Nov 1;15(21):6560-9. doi: 10.1158/1078-0432.CCR-09-1066. Epub 2009 Oct 27.
2
Gain or loss of TGFbeta signaling in mammary carcinoma cells can promote metastasis.乳腺癌细胞中转化生长因子β（TGFβ）信号的获得或丧失可促进转移。
Cell Cycle. 2009 Oct 15;8(20):3319-27. doi: 10.4161/cc.8.20.9727. Epub 2009 Oct 4.
3
Platelet-derived transforming growth factor-beta down-regulates NKG2D thereby inhibiting natural killer cell antitumor reactivity.血小板衍生的转化生长因子-β下调NKG2D，从而抑制自然杀伤细胞的抗肿瘤反应性。
Cancer Res. 2009 Oct 1;69(19):7775-83. doi: 10.1158/0008-5472.CAN-09-2123. Epub 2009 Sep 8.
4
Polarization of tumor-associated neutrophil phenotype by TGF-beta: "N1" versus "N2" TAN.转化生长因子-β对肿瘤相关中性粒细胞表型的极化作用：“N1”与“N2”肿瘤相关中性粒细胞
Cancer Cell. 2009 Sep 8;16(3):183-94. doi: 10.1016/j.ccr.2009.06.017.
5
The yin-yang of tumor-associated neutrophils.肿瘤相关中性粒细胞的阴阳学说
Cancer Cell. 2009 Sep 8;16(3):173-4. doi: 10.1016/j.ccr.2009.08.014.
6
Inhibition of transforming growth factor-beta-mediated immunosuppression in tumor-draining lymph nodes augments antitumor responses by various immunologic cell types.抑制肿瘤引流淋巴结中转化生长因子-β介导的免疫抑制可增强多种免疫细胞类型的抗肿瘤反应。
Cancer Res. 2009 Jun 15;69(12):5142-50. doi: 10.1158/0008-5472.CAN-08-2499. Epub 2009 Jun 2.
7
Mechanisms of foxp3+ T regulatory cell-mediated suppression.Foxp3+调节性T细胞介导的抑制机制。
Immunity. 2009 May;30(5):636-45. doi: 10.1016/j.immuni.2009.04.010.
8
Abrogation of TGF-beta signaling enhances chemokine production and correlates with prognosis in human breast cancer.转化生长因子-β信号的消除增强趋化因子的产生，并与人类乳腺癌的预后相关。
J Clin Invest. 2009 Jun;119(6):1571-82. doi: 10.1172/JCI37480. Epub 2009 May 18.
9
A Mutant-p53/Smad complex opposes p63 to empower TGFbeta-induced metastasis.一种突变型p53/Smad复合物对抗p63以增强TGFβ诱导的转移。
Cell. 2009 Apr 3;137(1):87-98. doi: 10.1016/j.cell.2009.01.039.
10
Trophic macrophages in development and disease.发育和疾病中的营养性巨噬细胞。
Nat Rev Immunol. 2009 Apr;9(4):259-70. doi: 10.1038/nri2528.
Zotero 插件