The Fas counterattack: Fas-mediated T cell killing by colon cancer expressing Fas ligand

Abstract

Tumors escape immunologically rejection by a diversity of mechanisms. In this report, we demonstrate that the colon cancer cell SW620 expresses functional Fas ligand (FasL), the triggering agent of fas receptor (FasR)- mediated apoptosis within the immune system. FasL and cell mRNA and cell surfaces FasL were detected in SW20 cells using reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemical staining, respectively. We show that WS620 kills Jurkat T cells in a Fas-mediated manner. FasR-specific antisense oligonucleotide treatment, which transiently inhibited FasR expression, completely protected jurkat cells from killing by SW620. FasL-specific antisense oligonucleotide treatment of SW620 inhibited its Jurkat-killing activity. FasL has recently been established as a mediator of immune privilege in mouse retina and rests. Our finding that colon cancer cells express functional FasL suggest it may play an analogous role in bestowing immune privilege on human tumors. HT29 and SW620 colon cancer cells were found to express FasR mRNA and cell surface FasR using RT-PCR and immunofluorescence flow cytometry, respectively. However, neither of these cells underwent apoptosis after treatment by the anti-FasR agonistic monoclonal antibody Ch11. Our results therefore suggest a Fas counterattack model for immune escape express functional FasR, an apoptotic death signal to which activated T cells are inherently sensitive.