Functional characterization of Fas ligand on tumor cells escaping active specific immunotherapy.
Mice transgenic for the rat HER-2/neu oncogene (rNeu-TG) developed spontaneous breast tumors that can escape a rNeu-specific immune response induced by active specific immunotherapy (ASI). The ability of these escape tumors to grow appeared to be due to upregulation of the Fas ligand (Fas-L) molecule. In an effort to develop tools for the better elucidation of the role of Fas-L and other regulatory mechanisms in tumor escape, we established cell lines derived from escape tumors. These tumor cell lines retained MHC class I, rNeu and Fas-L expression in vitro and formed tumors in vaccinated mice. Tumor growth was accompanied by permanent Fas-L expression in vivo, both in vaccinated and control vaccinated mice, indicating that these cells have acquired constitutive Fas-L expression. Moreover, these cells induced target cell apoptosis in vitro. Thus, these cells represent a unique tool to elucidate the importance of Fas-L expressed by tumors that escaped efficient systemic immune responses.
Céfai
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Department of Clinical Research, University of Bern, 35 Murtenstrasse, 3010 Bern, Switzerland.
Schwaninger
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Balli
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Brunner
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Gimmi
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D016475:3T3 Cells; D000230:Adenocarcinoma / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000628:therapy; D000818:Animals; D017209:Apoptosis; D018920:Coculture Techniques; D053222:Fas Ligand Protein; D005434:Flow Cytometry; D015870:Gene Expression; D007150:Immunohistochemistry; D016233:Immunotherapy, Active; D015674:Mammary Neoplasms, Animal / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000628:therapy*; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D009368:Neoplasm Transplantation; D010641:Phenotype; D051381:Rats; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014611:Vaccination
D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D018719:Erb-b2 Receptor Tyrosine Kinases; C505658:Fasl protein, mouse; C505662:Faslg protein, rat