Expression of GARP Is Increased in Tumor-Infiltrating Regulatory T Cells and Is Correlated to Clinicopathology of Lung Cancer Patient

被引:21
作者
Jin, Hao [1 ,2 ,3 ]
Sun, Liping [1 ,2 ,3 ]
Tang, Lu [4 ]
Yu, Wenwen [1 ,2 ,3 ]
Li, Hui [2 ,3 ,5 ]
机构
[1] Tianjin Med Univ Canc Inst & Hosp, Dept Immunol, Tianjin, Peoples R China
[2] Key Lab Canc Immunol & Biotherapy, Tianjin, Peoples R China
[3] Natl Clin Res Ctr Canc, Tianjin, Peoples R China
[4] Tianjin First Ctr Hosp, Div Rheumatol, Tianjin, Peoples R China
[5] Tianjin Med Univ Canc Inst & Hosp, Dept Gastrointestinal Canc Biol, Tianjin, Peoples R China
来源
FRONTIERS IN IMMUNOLOGY | 2017年 / 8卷
基金
中国国家自然科学基金;
关键词
lung cancer; regulatory T cells; GAR P; TGF-beta; Foxp3; LAP; clinicopathology; LATENT TGF-BETA; FOXP3; EXPRESSION; TRANSFORMING GROWTH-FACTOR-BETA-1; PERIPHERAL-BLOOD; LYMPHOCYTES; CARCINOMA; SURFACE; MICROENVIRONMENT; DIFFERENTIATION; RECRUITMENT;
D O I
10.3389/fimmu.2017.00138
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Regulatory T cells (Tregs) are immunosuppressive T cells that play an important role in immune homeostasis. Multiple markers have been associated with the characterization, as well as function of Tregs. Recently, glycoprotein A repetitions predominant (GARP), a transmembrane protein containing leucine-rich repeats, has been found to be highly expressed on the surface of activated Tregs. GARP maintains Tregs' regulatory function and homeostasis through the activation and secretion of transforming growth factor beta. In this study, we investigated the expression of GARP in Tregs from the peripheral blood (PB) and tumor tissues of lung cancer patients. The association between the proportion and expression level of GARP on Tregs and the clinicopathological factors of lung cancer patients was also analyzed. Results showed that in the tumor tissues of patients with lung cancer, GARP expression was increased in Tregs and was associated with lymph node metastasis, distant metastasis, and clinical stage. Furthermore, the infiltrating Tregs from early stage patients exhibited higher GARP expression than that from advanced cancer patients, which indicated that GARP might be an early prognostic biomarker. In vitro coculture studies demonstrated that human lung cancer cell lines might induce the expression of GARP in Tregs by certain mechanisms. Overall, this research demonstrated the potential value of GARP in Tregs definition and cancer immunotherapy.
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页数:11
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共 36 条
[1]   Inhibition of human CD4+CD25+high regulatory T cell function [J].
Baecher-Allan, C ;
Viglietta, V ;
Hafler, DA .
JOURNAL OF IMMUNOLOGY, 2002, 169 (11) :6210-6217
[2]   The molecular structure of the Toll-like receptor 3 ligand-binding domain [J].
Bell, JK ;
Botos, I ;
Hall, PR ;
Askins, J ;
Shiloach, J ;
Segal, DM ;
Davies, DR .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2005, 102 (31) :10976-10980
[3]   LAG-3 Expression Defines a Subset of CD4+CD25highFoxp3+ Regulatory T Cells That Are Expanded at Tumor Sites [J].
Camisaschi, Chiara ;
Casati, Chiara ;
Rini, Francesca ;
Perego, Michela ;
De Filippo, Annamaria ;
Rini, Frederic ;
Parmiani, Giorgio ;
Belli, Filiberto ;
Rivoltini, Licia ;
Castelli, Chiara .
JOURNAL OF IMMUNOLOGY, 2010, 184 (11) :6545-6551
[4]   Resolving the identity myth: Key markers of functional CD4+FoxP3+ regulatory T cells [J].
Chen, Xin ;
Oppenheim, Joost J. .
INTERNATIONAL IMMUNOPHARMACOLOGY, 2011, 11 (10) :1489-1496
[5]   Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival [J].
Curiel, TJ ;
Coukos, G ;
Zou, LH ;
Alvarez, X ;
Cheng, P ;
Mottram, P ;
Evdemon-Hogan, M ;
Conejo-Garcia, JR ;
Zhang, L ;
Burow, M ;
Zhu, Y ;
Wei, S ;
Kryczek, I ;
Daniel, B ;
Gordon, A ;
Myers, L ;
Lackner, A ;
Disis, ML ;
Knutson, KL ;
Chen, LP ;
Zou, WP .
NATURE MEDICINE, 2004, 10 (09) :942-949
[6]   Regulation of the Expression of GARP/Latent TGF-β1 Complexes on Mouse T Cells and Their Role in Regulatory T Cell and Th17 Differentiation [J].
Edwards, Justin P. ;
Fujii, Hodaka ;
Zhou, Angela X. ;
Creemers, John ;
Unutmaz, Derya ;
Shevach, Ethan M. .
JOURNAL OF IMMUNOLOGY, 2013, 190 (11) :5506-5515
[7]   Increase of regulatory T cells in metastatic stage and CTLA-4 over expression in lymphocytes of patients with non-small cell lung cancer (NSCLC) [J].
Erfani, Nasrollah ;
Mehrabadi, Shayesteh Mofakhami ;
Ghayumi, Mohammad Ali ;
Haghshenas, Mohammad Reza ;
Mojtahedi, Zahra ;
Ghaderi, Abbas ;
Amani, Davar .
LUNG CANCER, 2012, 77 (02) :306-311
[8]   Regulatory T cell lineage specification by the forkhead transcription factor FoxP3 [J].
Fontenot, JD ;
Rasmussen, JP ;
Williams, LM ;
Dooley, JL ;
Farr, AG ;
Rudensky, AY .
IMMUNITY, 2005, 22 (03) :329-341
[9]  
Gavin MA, 2006, P NATL ACAD SCI USA, V103, P6659, DOI 10.1073/pnas.0509484103
[10]   High expression of FOXP3 in primary melanoma is associated with tumour progression [J].
Gerber, A. L. ;
Muenst, A. ;
Schlapbach, C. ;
Shafighi, M. ;
Kiermeir, D. ;
Huesler, R. ;
Hunger, R. E. .
BRITISH JOURNAL OF DERMATOLOGY, 2014, 170 (01) :103-109