TGF-β and immune cells: an important regulatory axis in the tumor microenvironment and progression

被引:772
作者
Yang, Li [1 ]
Pang, Yanli [1 ]
Moses, Harold L. [2 ]
机构
[1] NCI, Lab Canc Biol & Genet, Ctr Canc Res, NIH, Bethesda, MD 20876 USA
[2] Vanderbilt Univ, Sch Med, Dept Canc Biol, Vanderbilt Ingram Canc Ctr, Nashville, TN 37232 USA
关键词
GROWTH-FACTOR-BETA; NF-KAPPA-B; T-CELLS; MYELOID CELLS; COLON-CANCER; PROMOTE METASTASIS; LUNG METASTASIS; BREAST-CANCER; IN-VIVO; INFLAMMATION;
D O I
10.1016/j.it.2010.04.002
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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 miwcroenvironment 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.
引用
收藏
页码:220 / 227
页数:8
相关论文
共 86 条
[1]   A Mutant-p53/Smad Complex Opposes p63 to Empower TGFβ-Induced Metastasis [J].
Adorno, Maddalena ;
Cordenonsi, Michelangelo ;
Montagner, Marco ;
Dupont, Sirio ;
Wong, Christine ;
Hann, Byron ;
Solari, Aldo ;
Bobisse, Sara ;
Rondina, Maria Beatrice ;
Guzzardo, Vincenza ;
Parenti, Anna R. ;
Rosato, Antonio ;
Bicciato, Silvio ;
Balmain, Allan ;
Piccolo, Stefano .
CELL, 2009, 137 (01) :87-98
[2]   TGF-β signaling in cancer -: a double-edged sword [J].
Akhurst, RJ ;
Derynck, R .
TRENDS IN CELL BIOLOGY, 2001, 11 (11) :S44-S51
[3]  
Almand B, 2000, CLIN CANCER RES, V6, P1755
[4]   Inhibition of TGFβ signaling in cancer therapy [J].
Arteaga, CL .
CURRENT OPINION IN GENETICS & DEVELOPMENT, 2006, 16 (01) :30-37
[5]   Cancer - An inflammatory link [J].
Balkwill, F ;
Coussens, LM .
NATURE, 2004, 431 (7007) :405-406
[6]   TH-17 cells in the circle of immunity and autoimmunity [J].
Bettelli, Estelle ;
Oukka, Mohamed ;
Kuchroo, Vijay K. .
NATURE IMMUNOLOGY, 2007, 8 (04) :345-350
[7]   TGF-β signaling in fibroblasts modulates the oncogenic potential of adjacent epithelia [J].
Bhowmick, NA ;
Chytil, A ;
Plieth, D ;
Gorska, AE ;
Dumont, N ;
Shappell, S ;
Washington, MK ;
Neilson, EG ;
Moses, HL .
SCIENCE, 2004, 303 (5659) :848-851
[8]   Transforming growth factor-β regulates mammary carcinoma cell survival and interaction with the adjacent microenvironment [J].
Bierie, Brian ;
Stover, Daniel G. ;
Chytil, Anna ;
Gorska, Agnieszka E. ;
Aakre, Mary ;
Forrester, Elizabeth ;
Yang, Li ;
Wagner, Kay-Uwe ;
Moses, Harold L. .
CANCER RESEARCH, 2008, 68 (06) :1809-1819
[9]   TGFβ:: the molecular Jekyll and Hyde of cancer [J].
Bierie, Brian ;
Moses, Harold L. .
NATURE REVIEWS CANCER, 2006, 6 (07) :506-520
[10]   Gain or loss of TGFβ signaling in mammary carcinoma cells can promote metastasis [J].
Bierie, Brian ;
Moses, Harold L. .
CELL CYCLE, 2009, 8 (20) :3319-3327