TGF-β of lung cancer microenvironment upregulates B7H1 and GITRL expression in dendritic cells and is associated with regulatory T cell generation

被引:94
作者
Ni, Xiao Yan [1 ]
Sui, Hua Xiu [1 ]
Liu, Yao [1 ]
Ke, Shi Zhong [1 ]
Wang, Yi Nan [1 ]
Gao, Feng Guang [1 ,2 ]
机构
[1] Xiamen Univ, Coll Med, Dept Immunol, Xiamen 361005, Peoples R China
[2] Jiao Tong Univ, Canc Inst Shanghai, State Key Lab Oncogenes & Related Genes, Shanghai 200030, Peoples R China
关键词
regulatory T cells; dendritic cells; B7H1; GITRL; tumor microenvironment; TUMOR MICROENVIRONMENT; GROWTH; EXPANSION; STIMULATE; SYSTEM; STROMA;
D O I
10.3892/or.2012.1822
中图分类号
R73 [肿瘤学];
学科分类号
100214 [肿瘤学];
摘要
The effects of TGF-beta on dendritic cells (DCs) on the tumor microenvironment are not well understood. We report, here, the establishment of an in vitro lung cancer microenvironment by co-incubation of seminaphtharho-dafluor (SNARE) labeled Lewis lung cancer (LLC) cells, carboxyfluorescein succinimidyl ester (CFSE) labeled fibroblasts and 4-chloromethyl-7-hydroxycoumarin (CM HC) labeled DCs. Raw 264.7, EL4 and NCI-H446 cells were able to synthesize TGF-beta which was determined by flow cytometry and western blotting, respectively. Furthermore, TGF-beta efficiently increased regulatory T-cell (Treg) expansion and upregulated DC B7H1 and GITRL expression. TGF-beta and the co-incubation of LLC cells, fibroblasts with DCs could augment the expression of B7H1 and GITRL molecules of DCs. The data presented here indicate that the B7H1 and GITRL molecules may play an important role in TGF-beta-induced Treg expansion of lung cancer microenvironment.
引用
收藏
页码:615 / 621
页数:7
相关论文
共 34 条
[1]
IFN-γ, IL-17 and TGF-β involvement in shaping the tumor microenvironment: The significance of modulating such cytokines in treating malignant solid tumors [J].
Alshaker, Heba A. ;
Matalka, Khalid Z. .
CANCER CELL INTERNATIONAL, 2011, 11
[2]
BARSKY SH, 1984, AM J PATHOL, V115, P329
[3]
All-trans retinoic acid mediates enhanced T reg cell growth, differentiation, and gut homing in the face of high levels of co-stimulation [J].
Benson, Micah J. ;
Pino-Lagos, Karina ;
Rosemblatt, Mario ;
Noelle, Randolph J. .
JOURNAL OF EXPERIMENTAL MEDICINE, 2007, 204 (08) :1765-1774
[4]
Expansion and characteristics of human T regulatory type 1 cells in co-cultures simulating tumor microenvironment [J].
Bergmann, Christoph ;
Strauss, Laura ;
Zeidler, Reinhard ;
Lang, Stephan ;
Whiteside, Theresa L. .
CANCER IMMUNOLOGY IMMUNOTHERAPY, 2007, 56 (09) :1429-1442
[5]
Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells [J].
Bettelli, E ;
Carrier, YJ ;
Gao, WD ;
Korn, T ;
Strom, TB ;
Oukka, M ;
Weiner, HL ;
Kuchroo, VK .
NATURE, 2006, 441 (7090) :235-238
[6]
Adaptive Foxp3+ regulatory T cell-dependent and -independent control of allergic inflammation [J].
de Lafaille, Maria A. Curotto ;
Kutchukhidze, Nino ;
Shen, Shiqian ;
Ding, Yi ;
Yee, Herman ;
Lafaille, Juan J. .
IMMUNITY, 2008, 29 (01) :114-126
[7]
Nicotine Stimulated Dendritic Cells Could Achieve Anti-Tumor Effects in Mouse Lung and Liver Cancer [J].
Gao, Feng Guang ;
Li, Hai Tao ;
Li, Zhi Jing ;
Gu, Jian Ren .
JOURNAL OF CLINICAL IMMUNOLOGY, 2011, 31 (01) :80-88
[8]
Dysfunction of murine dendritic cells induced by incubation with tumor cells [J].
Gao, Fengguang ;
Hui, Xin ;
He, Xianghuo ;
Wan, Dafang ;
Gu, Jianren .
CELLULAR & MOLECULAR IMMUNOLOGY, 2008, 5 (02) :133-140
[9]
Transgenic mice expressing a dominant-negative mutant type II transforming growth factor-b receptor exhibit impaired mammary development and enhanced mammary tumor formation [J].
Gorska, AE ;
Jensen, RA ;
Shyr, Y ;
Aakre, ME ;
Bhowmick, NA ;
Moses, HL .
AMERICAN JOURNAL OF PATHOLOGY, 2003, 163 (04) :1539-1549
[10]
Hakkinen L, 2011, METHODS CELL SCI, V23, P189