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

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 synge neic 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 elici ted 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 resu lts suggest that the transduced 4-1 BBL is more effective than the spontane ously expressed CD80 for generation of primary anti-tumour CD8(+) T-cell re sponses. In addition to CD80 and CD86, the host-derived 4-1BBL is also invo lved in the secondary anti-tumour responses. This study indicates the compl icated contribution of 4-1BBL, CD80 and CD86 on tumour and host cells in an ti-tumour immune responses and a possible therapeutic application of 4-1BBL for human tumour vaccination and gene therapy.