Tumour rejection by gene transfer of 4-1BB ligand into a CD80(+) murine squamous cell carcinoma and the requirements of co-stimulatory molecules on tumour and host cells

• Published in: Immunology Vol. 101; no. 4; pp. 541 - 547
• Main Authors: Mogi, S, Sakurai, J, Kohsaka, T, Enomoto, S, Yagita, H, Okumura, K, Azuma, M
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 01.12.2000; Blackwell Science Inc
• Subjects: 4-1BB Ligand; Animals; Antigens, CD - immunology; Antigens, Neoplasm - immunology; B7-1 Antigen - immunology; B7-2 Antigen; Carcinoma, Squamous Cell - immunology; Carcinoma, Squamous Cell - pathology; Carcinoma, Squamous Cell - therapy; CD8-Positive T-Lymphocytes - immunology; Female; Gene Transfer Techniques; Graft Rejection - immunology; Ligands; Membrane Glycoproteins - immunology; Mice; Mice, Inbred BALB C; Mice, Inbred C3H; Mice, Nude; Neoplasm Transplantation; Original; Transduction, Genetic; Transfection; Tumor Cells, Cultured; Tumor Necrosis Factor-alpha - genetics; Tumor Necrosis Factor-alpha - immunology
• ISSN: 0019-2805; 1365-2567
• DOI: 10.1046/j.1365-2567.2000.t01-1-00138.x

NRS1 is a murine squamous cell carcinoma that constitutively expresses the co-stimulatory molecule CD80 at a high level yet grows as a tumour in syngeneic C3H mice. We examined the effect of gene transfer of the 4-1BB ligand (4-1BBL) into NRS1 cells. Introduction of the 4-1BBL gene efficiently elicited anti-tumour immune responses in syngeneic mice which acquired specific immunity against wild-type tumour. T-cell depletion studies showed that CD8(+), but not CD4(+) T cells were essential for tumour eradication. Our results suggest that the transduced 4-1BBL is more effective than the spontaneously expressed CD80 for generation of primary anti-tumour CD8(+) T-cell responses. In addition to CD80 and CD86, the host-derived 4-1BBL is also involved in the secondary anti-tumour responses. This study indicates the complicated contribution of 4-1BBL, CD80 and CD86 on tumour and host cells in anti-tumour immune responses and a possible therapeutic application of 4-1BBL for human tumour vaccination and gene therapy.