Abstract
Objective
THANK, known as a member of TNF superfamily, is a potent costimulator of both B and T lymphocytes and can promote a strong immune response. To investigate its role in liver immunotherapy, the anti-tumor effects of the THANK-transduced hepatoma cell line SMMU-7721 in vitro and in vivo were studied.
Methods
THANK full-length cDNA was transfected into SMMU-7721 cell line. The transfectant with stable expression of THANK was obtained by clone selection and THANK's effects on hepatoma cells were analyzed, further the tumorigenicity of THANK-transduced 7721 cells was examined in nude mice.
Results
THANK's expression in 7721 cells inhibited the growth of hepatoma cells and induced a strong CTL response in vitro. The cell cycle analysis showed that THANK transfected 7721 cells were arrested in the S phase. The expression of THANK in SMMU-7721 cell line not only inhibited the tumorigenicity of 7721 cells, but also induced a systemic immune response against re-challenge of parental 7721 tumors.
Conclusion
THANK transduction in SMMU-7721 cells can induce an effective immune response in nude mice and may be useful for the immunotherapy of hepatomas.
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References
Jones RL, Young LS, Adams DH. Immunotherapy in hepatocellular carcinoma. Lancet, 2000, 356(9232): 784–785.
Mogi S, Sakurai J, Kohsaka T, et al. Tumor rejection by gene transfer of 4-IBB ligand into a CD80 (+) murine squamous cell carcinoma and the requirements of co-stimulatory molecules on tumour and host cells. Immunology, 2000, 101(4): 541–547.
Lu Y, Yamauchi N, Koshita Y, et al. Administration of subtumor regression dosage of TNF-alpha to mice with pre-existing parental tumors augments the vaccination effect of TNF gene-modified tumor through the induction of MHC class I molecule. Gene Ther, 2001, 8(7): 499–507.
Mukhopadhyay A, Ni J, Zhai Y, et al. Identification and characterization of a novel cytokine THANK: a TNF homologue that activates apoptosis, nuclear factor-kappaB, and c-Jun NH2-terminal kinase. J Biol Chem, 1999, 274 (23): 15978–15981.
Schneider P, MacKay F, Steiner V, et al. BAFF, a novel ligand of the tumor necrosis factor family, stimulates B cell growth. J Exp Med, 1999, 189 (11): 1747–1756.
Mackay F, Woodcock SA, Lawton P, et al. Mice transgenic for BAFF develop lymphocytic disorders along with autoimmune manifestations. J Exp Med, 1999, 190: 1697–1710.
Shu HB, Hu WH, Johnson H, et al. TALL-1 is a novel member of the TNF family that is down-regulated by mitogens. J Leukoc Biol, 1999, 65(5): 680–683.
Moore PA, Belvedere O, Orr A, et al. Blys: member of the tumor necrosis factor family and B lymphocyte stimulator. Science, 1999, 285(5425): 260–263.
Mackay F, Woodcock SA, Lawton P, et al. TACI and BCMA are receptors for a TNF homologue implicated in B-cell autoimmune disease. Nature, 2000, 404 (6781): 995–999.
Yu G, Boone T, Delaney J, et al. APRIL and TALL-I and receptors BCMA and TACI: system for regulating humoral immunity. Nat Immunol, 2000, 1: 252–256.
Huard B, Schneider P, Mauri D, et al. T Cell costimulation by the TNF ligand BAFF. J Immunol, 2001, 167(11): 6225–6231.
Von Bulow G, van Deursen JM, Bram RJ. Regulation of the T-independent humoral response by taci. Immunity, 2001, 14(5): 573–582.
Yan M, Wang H, Chan B, et al. Activation and accumulation of B cells in TACI-deficient mice. Nat Immunol, 2001, 2: 638–643.
Wang H, Marsters SA, Baker T, et al. TACI-ligand interactions are required for T cell activation and collagen-induced arthritis in mice. Nat Immunol, 2001, 2: 632–637.
Von Bulow G, van Deursen JM, Bram RJ. Regulation of the t-independent humoral response by taci. Immunity, 2001, 14: 573–582.
Wu D, Shen F, Lou YH, et al. The gene cloning and expression of THANK. Chinese J Microbiol and Immunol, 2001, 21(4): 460–464
Zhang J, Roschke V, Baker KP, et al. A role for B lymphocyte stimulator in systemic lupus erythematosus. J Immunol, 2001, 166 (1): 6–10.
Khare SD, Hsu H. The role of TALL-1 and APRIL in immune regulation. Trends Immunol, 2001, 2(2): 61–63.
Yan M, Marsters SA, Grewal IS, et al. Identification of a receptor for Blys demonstrates a crucial role in humoral immunity. Nat Immunol, 2000, 1: 37–41.
Ware CF. APRIL and BAFF connect autoimmunity and cancer. J Exp Med, 2000, 192 (11): 35–8.
Thompson JS, Schneider P, Kalled SL, et al. BAFF binds to the tumor necrosis factor receptor-like molecule B cell maturation antigen and is important for maintaining the peripheral B cell population. J Exp Med, 2000, 192(1): 129–136.
Marsters SA, Yan M, Pitti RM, et al. Interaction of the TNF homologues Blys and APRIL with the TNF receptor homologues BCMA and TACI. Curr Biol, 2000, 10 (13): 785–788.
Xu S, Lam KP. B-cell maturation protein, which binds the tumor necrosis factor family members BAFF and APRIL, is dispensable for humoral immune responses. Mol Cell Biol, 2001, 21(12): 4067–4074.
Wu Y, Bressette D, Carrell JA, et al. Tumor necrosis factor (TNF) receptor superfamily member TACI is a high affinity receptor for TNF family members APRIL and Blys. J Biol Chem, 2000, 275(45): 35478–35485.
Nardelli B, Belvedere O, Roschke V, et al. Synthesis and release of B-lymphocyte stimulator from myeloid cells. Blood, 2001, 97 (1): 198–204.
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Wu, D., Shen, F. & Wu, M. In vitro and in vivo study of the antitumor effects of a THANK modified hepatoma cell line. Chin. -Ger. J. Clin. Oncol. 1, 78–83 (2002). https://doi.org/10.1007/BF02851739
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DOI: https://doi.org/10.1007/BF02851739