The T cell death knell: immune-mediated tumor death in renal cell carcinoma
| Autor: | R G, Uzzo, V, Kolenko, C J, Froelich, C, Tannenbaum, L, Molto, A C, Novick, N H, Bander, R, Bukowski, J H, Finke |
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| Rok vydání: | 2001 |
| Předmět: |
Pore Forming Cytotoxic Proteins
Caspase 8 Fas Ligand Protein Membrane Glycoproteins Perforin Fas-Associated Death Domain Protein Serine Endopeptidases Antibodies Monoclonal Apoptosis Caspase 9 Granzymes Enzyme Activation Jurkat Cells Necrosis Drug Resistance Neoplasm Caspases Tumor Cells Cultured Humans fas Receptor Carrier Proteins Carcinoma Renal Cell Adaptor Proteins Signal Transducing T-Lymphocytes Cytotoxic |
| Zdroj: | Clinical cancer research : an official journal of the American Association for Cancer Research. 7(10) |
| ISSN: | 1078-0432 |
| Popis: | The antitumor effect of T cells is executed either through CD95 or Perforin (PFN)/Granzyme B (GrB) pathways. Induction of apoptosis by either mode requires activation of caspase family members. However, recent studies have suggested that cell death can proceed in the absence of caspase induction and apoptotic events. We investigated the contribution of CD95 and PFN/GrB-mediated cytotoxicity to apoptotic and necrotic mechanisms of cell death in human renal cell carcinoma. Although freshly isolated and cultured tumors expressed CD95 on their surface, they were resistant to CD95-mediated apoptosis. CD95 resistance coincided with decreased levels of FADD protein and diminished caspase-3-like activity. In contrast, we demonstrated that tumor cell death mediated by PFN/GrB can be achieved in the absence of functional caspase activity and is accompanied by a dramatic accumulation of nonapoptotic necrotic cells. |
| Databáze: | OpenAIRE |
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