Decreased sensitivity of drug-resistant cells towards T cell cytotoxicity

Citation
Cf. Classen et al., Decreased sensitivity of drug-resistant cells towards T cell cytotoxicity, LEUKEMIA, 13(3), 1999, pp. 410-418
Citations number
40
Categorie Soggetti
Onconogenesis & Cancer Research
Journal title
LEUKEMIA
ISSN journal
08876924 → ACNP
Volume
13
Issue
3
Year of publication
1999
Pages
410 - 418
Database
ISI
SICI code
0887-6924(199903)13:3<410:DSODCT>2.0.ZU;2-Y
Abstract
Killing of target cells by cytotoxic T cells is mediated by induction of ap optosis requiring functional death pathways. Kill is mediated either by the CD95 or the perforin/granzyme pathway. We found that SH-EP neuroblastoma c ells are preferentially kilted via CD95, while in the T leukemia cell line CEM CD95 and perforin/granzyme are involved. In both types of cell lines, c ells resistant to CD95- and drug-induced apoptosis are cross-resistant to c ytotoxic T cell kill. Resistant cells show decreased apoptosis and deficien t activation of caspases indicated by decreased cleavage of the prototype c aspase substrate PARP. Preincubation with the caspase inhibitor zVAD-fmk st rongly decreased LAK cell kill in sensitive cells. Although parental CEM ce lls could be sensitized for LAK kill by preincubation with doxorubicin, res istance could not be reverted in doxorubicin or CD95 resistant CEM cells. T hese data demonstrate the crossresistance in induction of apoptosis by diff erent cytotoxic regimens in tumor cells and may have implications for the i mmunotherapy of tumors in which apoptosis resistance was induced by previou s chemotherapy.