| First Author | Medema JP | Year | 1999 |
| Journal | J Exp Med | Volume | 190 |
| Issue | 7 | Pages | 1033-8 |
| PubMed ID | 10510093 | Mgi Jnum | J:115086 |
| Mgi Id | MGI:3690656 | Doi | 10.1084/jem.190.7.1033 |
| Citation | Medema JP, et al. (1999) Immune escape of tumors in vivo by expression of cellular FLICE-inhibitory protein. J Exp Med 190(7):1033-8 |
| abstractText | The antiapoptotic protein cellular FLICE (Fas-associated death domain-like IL-1beta-converting enzyme) inhibitory protein (cFLIP) protects cells from CD95(APO-1/Fas)-induced apoptosis in vitro and was found to be overexpressed in human melanomas. However, cytotoxic T cell-induced apoptosis, which is critically involved in tumor control in vivo, is not inhibited by cFLIP in vitro, as only CD95- and not perforin-dependent lysis is affected. This calls into question whether cFLIP is sufficient to allow escape from T cell-dependent immunity. Using two murine tumors, we directly demonstrate that cFLIP does result in escape from T cell immunity in vivo. Moreover, tumor cells are selected in vivo for elevated cFLIP expression. Therefore, our data indicate that CD95-dependent apoptosis constitutes a more prominent mechanism for tumor clearance than has so far been anticipated and that blockade of this pathway can result in tumor escape even when the perforin pathway is operational. |
