|
|
4-1BBL expressed by eukaryotic cells activates immune cells and suppresses the progression of murine tumor |
Hui QIU1, Hui ZHANG2, Zuohua FENG2() |
1. Department of Oncology, Zhongnan Hospital, Wuhan University, Wuhan 430071, China; 2. Department of Biochemistry and Molecular Biology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China |
|
|
Abstract The interaction by co-stimulatory molecules 4-1BB and 4-1BB ligand (4-1BBL) plays an important role in the activation, proliferation and differentiation of T lymphocytes. The function of 4-1BB/4-1BBL expressed by the immune cells has been the focus for many tumor immunotherapy efforts. In this study, 4-1BBL was expressed in non-immune cells and non-tumor cells, and the role of 4-1BBL in lymphocyte activation and tumor suppression was investigated. The plasmid p4-1BBL containing the full length of mouse 4-1BBL cDNA sequence was constructed, and the plasmid was transfected into baby hamster kidney (BHK) cells and murine muscle cells by means of lipofectin-mediated or naked plasmid DNA injection into the muscle directly. The study demonstrated that the molecule 4-1BBL expressed by BHK cells in vitro could enhance the proliferation and cytotoxicity of lymphocytes, and it could increase the expression level of IL-2 and IFN-γ. The treatment with plasmid p4-1BBL in vivo revealed that the number of CD8+ T cells in the peri-tumoral tissue increased markedly, and the growth rate of the tumor was significantly lower than that of control group. These findings suggest that expression of 4-1BBL by normal cells in the tumor microenvironment can enhance the proliferation and other functions of T lymphocytes. This therapeutic method may provide a promising approach for tumor immunotherapy.
|
Keywords
4-1BB ligand
tumor immunotherapy
tumor microenvironment
|
Corresponding Author(s):
FENG Zuohua,Email:fengzhg@public.wh.hb.cn
|
Issue Date: 05 March 2009
|
|
1 |
Goodwin R G, Din W S, Davis-Smith T, Anderson D M, Gimpel S D, Sato T A, Maliszewski C R, Brannan C I, Copeland N G, Jenkins N A. Molecular cloning of a ligand for the inducible T cell gene 4-1BB: a member of an emerging family of cytokines with homology to tumor necrosis factor. Eur J Immuno , 1993, 23(10): 2631-2641 doi: 10.1002/eji.1830231037
|
2 |
Pollok K E, Kim Y J, Zhou Z, Hurtado J, Kim K K, Pickard R T, Kwon B S. Inducible T cell antigen 4-1BB. Analysis of expression and function. J Immunol , 1993, 150(3): 771-781
|
3 |
Wilcox R A, Chapoval A I, Gorski K S, Otsuji M, Shin T, Flies D B, Tamada K, Mittler R S, Tsuchiya H, Pardoll D M, Chen L. Cutting edge: expression of functional CD137 receptor by dendritic cells. J Immunol , 2002, 168(9): 4262-4267
|
4 |
DeBenedette M A, Shahinian A, Mak T W, Watts T H. Costimulation of CD28-T lymphocytes by 4-1BB ligand. J Immunol , 1997, 158(2): 551-559
|
5 |
Cannons J L, Lau P, Ghumman B, DeBenedette M A, Yagita H, Okumura K, Watts T H. 4-1BB ligand induces cell division, sustains survival, and enhances effector function of CD4 and CD8 T cells with similar efficacy. J Immunol , 2001, 167(3): 1313-1324
|
6 |
Shuford W W, Klussman K, Tritchler D D, Loo D T, Chalupny J, Siadak A W, Brown T J, Emswiler J, Raecho H, Larsen C P, Pearson T C, Ledbetter J A, Aruffo A, Mittler R S. 4-1BB costimulatory signals preferentially induce CD8+ T cell proliferation and lead to the amplification in vivo of cytotoxic T cell responses. J Exp Med , 1997, 186(1): 47-55 doi: 10.1084/jem.186.1.47
|
7 |
Saoulli K, Lee S Y, Cannons J L, Yeh W C, Santana A, Goldstein M D, Bangia N, DeBenedette M A, Mak T W, Choi Y, Watts T H. CD28-independent, TRAF2-dependent costimulation of resting T cells by 4-1BB ligand. J Exp Med , 1998, 187(11): 849-862 doi: 10.1084/jem.187.11.1849
|
8 |
Strome S E, Martin B, Flies D, Tamada K, Chapoval A I, Sargent DJ, Shu S, Chen L. Enhanced therapeutic potential of adoptive immunotherapy by in vitro CD28/4-1BB costimulation of tumor-reactive T cells against a poorly immunogenic, major histocompatibility complex class I-negative A9P melanoma. J Immunother , 2000, 23(4): 430-437 doi: 10.1097/00002371-200007000-00006
|
9 |
Xiang J. Expression of co-stimulatory 4-1BB ligand induces significant tumor regression and protective immunity. Cancer Biother Radiopharm , 1999, 14(5): 353-361 doi: 10.1089/cbr.1999.14.353
|
10 |
O'Driscoll L, Daly C, Saleh M, Clynes M. The use of reverse transcriptase-polymerase chain reaction (RT-PCR) to investigate specific gene expression in multidrug-resistant cells. Cytotechnology , 1993, 12(1-3): 289-314 doi: 10.1007/BF00744669
|
11 |
Lee N, Zhang S Q, Testa D. A rapid multicolor Western blot. J Immunol Methods , 1988, 106(1): 27-30 doi: 10.1016/0022-1759(88)90267-0
|
12 |
Schmidt-Kastner R, Meller D, Bellander B M, Str?mberg I, Olson L, Ingvar M. A one-step immunohistochemical method for detection of blood-brain barrier disturbances for immunoglobulins in lesioned rat brain with special reference to false-positive labeling in immunohistochemistry. J Neurosci Methods , 1993, 46(2): 121-132 doi: 10.1016/0165-0270(93)90147-J
|
13 |
Feng Z, Huang B, Zhang G, Li D, Wang H. Investigation on the effect of peptides mixture from tumor cells inducing anti-tumor specific immune response. Sci China C Life Sci , 2002, 45(4): 361-369 doi: 10.1360/02yc9040
|
14 |
Blachere N E, Li Z, Chandawarkar R Y, Suto R, Jaikaria N S, Basu S, Udono H, Srivastava P K. Heat shock protein-peptide complexes reconstituted in vitro, elicit peptide-specific cytotoxic T lymphocyte response and tumor immunity. J Exp Med , 1997, 186(8): 1315-1322 doi: 10.1084/jem.186.8.1315
|
15 |
Huang B, Feng Z, Zhang G, Li D, Wang H. Hsp70-H22 tumor antigen peptide complex activated dendritic cell in the induction of antitumor immunity. Zhonghua Zhong Liu Za Zhi , 2002, 24(5): 421-425 (in Chinese)
|
16 |
Ferrari M, Fornasiero M C, Isetta A M. MTT colorimetric assay for testing macrophage cytotoxic activity in vitro. J Immunol Methods , 1990, 131(2): 165-172 doi: 10.1016/0022-1759(90)90187-Z
|
17 |
Feng Z, Zhang G, Huang B, Li D, Wang H. Inducement of specific CTLs by antigen-peptides from human leukemia cells and their cytotoxicity to leukemia cells. J Huazhong Univ Sci Technol Med Sci , 2002, 22(4): 265-269
|
18 |
Kubota A, Lian R H, Lohwasser S, Salcedo M, Takei F. IFN-gamma production and cytotoxicity of IL-2-activated murine NK cells are differentially regulated by MHC class I molecules. J Immunol , 1999, 163(12): 6488-6493
|
19 |
Puliaev R, Nguyen P, Finkelman F D, Via C S. Differential requirement for IFN-gamma in CTL maturation in acute murine graft-versus-host disease. J Immunol , 2004, 173(2): 910-919
|
20 |
Langstein J, Becke F M, S?llner L, Krause G, Brockhoff G, Kreutz M, Andreesen R, Schwarz H. Comparative analysis of CD137 and LPS effects on monocyte activation, survival, and proliferation. Biochem Biophys Res Commun , 2000, 273(1): 117-122 doi: 10.1006/bbrc.2000.2889
|
21 |
Nam K O, Shin S M, Lee H W. Cross-linking of 4-1BB up-regulates IL-13 expression in CD8(+) T lymphocytes. Cytokine , 2006, 33(2): 87-94 doi: 10.1016/j.cyto.2005.12.003
|
22 |
Ju S A, Lee S C, Kwon T H, Heo S K, Park S M, Paek H N, Suh J H, Cho H R, Kwon B, Kwon B S, Kim B S. Immunity to melanoma mediated by 4-1BB is associated with enhanced activity of tumour-infiltrating lymphocytes. Immunol Cell Biol , 2005, 83(4): 344-351 doi: 10.1111/j.1440-1711.2005.01330.x
|
23 |
Lee H W, Park S J, Choi B K, Kim H H, Nam K O, Kwon B S. 4-1BB promotes the survival of CD8+ T lymphocytes by increasing expression of Bcl-xL and Bfl-1. J Immunol 2002, 169(9): 4882-4888
|
|
Viewed |
|
|
|
Full text
|
|
|
|
|
Abstract
|
|
|
|
|
Cited |
|
|
|
|
|
Shared |
|
|
|
|
|
Discussed |
|
|
|
|