title: Oral cancer cell lines can use multiple ligands, including Fas-L, TRAIL and TNF-alpha, to induce apoptosis in Jurkat T cells: possible mechanisms for immune escape by head and neck cancers.
abstract: Some cancer cells can induce apoptosis in tumour infiltrating cytotoxic T cells as a means of escaping immune destruction. This study examined the expression of the apoptosis-inducing ligands, Fas-L, TRAIL and TNF-alpha, on three representative oral squamous cell carcinoma (OSCC) cell lines, TR146, SCC25 and CAL27 and investigates the contribution of these ligands to tumour cell killing of Jurkat T cells in vitro. All three cell lines were able to induce apoptosis in Jurkat T cells to varying degrees. The TR146 cell line predominantly killed Jurkats via the well known Fas-L/Fas mediated pathway. Although TR146 also expressed low levels of TRAIL and TNF-alpha, these did not contribute significantly to TR146 killing of Jurkats. In contrast, the CAL27 cell line expressed little if any Fas-L but was still able to kill Jurkats effectively via an almost exclusively TRAIL mediated mechanism. The SCC25 cell line expressed significant levels of all three ligands but we were unable to significantly inhibit killing of Jurkats by blocking any one pathway with antibodies. SCC25 may use a combination of mechanisms to kill Jurkats and switch between them to compensate when one mechanism is blocked. We found that stimulation with interferon-gamma (IFN-gamma) induced or increased the expression of apoptosis-inducing ligands on OSCC as well as the killing of Jurkat T cells. Not only did IFN-gamma increase killing of Jurkats, but it changed the contribution of the Fas-L, TRAIL and TNF-alpha mediated mechanisms to the killing of Jurkat T cells by the different cell lines. These mechanisms if reproduced in vivo, could confer survival advantage on OSCC by enabling them to kill tumour invading cytotoxic lymphocytes and evade immune destruction.
authors.affiliation: Cardiovascular Division, King's College, London, UK.
authors.forename: Nick
authors.initials: N
authors.lastname: Kassouf
authors.forename: Martin H
authors.initials: MH
authors.lastname: Thornhill
mesh_terms: D017209:Apoptosis / Q000276:immunology; D002294:Carcinoma, Squamous Cell / Q000276:immunology*; D045744:Cell Line, Tumor; D053222:Fas Ligand Protein / Q000378:metabolism*; D005260:Female; D005434:Flow Cytometry; D006258:Head and Neck Neoplasms / Q000276:immunology*; D006801:Humans; D019169:Jurkat Cells; D008297:Male; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000378:metabolism*; D019139:Tumor Escape / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D053222:Fas Ligand Protein; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D014409:Tumor Necrosis Factor-alpha