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

Immunology. 2000 Dec;101(4):541-7. 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 4-1BB Ligand
  • Animals
  • Antigens, CD / immunology
  • Antigens, Neoplasm / immunology
  • B7-1 Antigen / immunology*
  • B7-2 Antigen
  • CD8-Positive T-Lymphocytes / immunology
  • Carcinoma, Squamous Cell / immunology*
  • Carcinoma, Squamous Cell / pathology
  • Carcinoma, Squamous Cell / therapy
  • Female
  • Gene Transfer Techniques
  • Graft Rejection / immunology*
  • Ligands
  • Membrane Glycoproteins / immunology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C3H
  • Mice, Nude
  • Neoplasm Transplantation
  • Transduction, Genetic
  • Transfection
  • Tumor Cells, Cultured
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / immunology*


  • 4-1BB Ligand
  • Antigens, CD
  • Antigens, Neoplasm
  • B7-1 Antigen
  • B7-2 Antigen
  • Cd86 protein, mouse
  • Ligands
  • Membrane Glycoproteins
  • TNFSF9 protein, human
  • Tnfsf9 protein, mouse
  • Tumor Necrosis Factor-alpha