Tumor cells undergoing programmed death are an attractive source of tumor-associated antigens, and evidences are available for their therapeutic efficacy in vivo when used either alone or in association with dendritic cells. However, little is known about the specificity of the immune response induced by such antigen formulation. Indeed, activation of specific proteases during apoptosis may influence the cytoplasmic degradation of proteins and the generation of CTL epitopes. We show here that on injection of C57BL/6 mice either with RMA lymphoma cells induced to apoptosis or bone marrow-derived dendritic cells pulsed with apoptotic RMA cells, a specific and protective CTL response is induced, which, however, is not directed against the immunodominant CTL epitope gag(85-93). Lack of in vivo expansion of gag(85-93)-specific CTL in vaccinated mice is attributable to the apoptosis-dependent loss of gag(85-93) in dying tumor cells. Indeed, we found loss of gag(85-93) in RMA, MBL-2, and EL-4G+ lymphoma cells, which share gag(85-93) as an immunodominant CTL epitope, induced to apoptosis by UV irradiation, mitomycin C, doxorubicin, or daunorubicin. This phenomenon appears to be caspase-dependent, because caspase inhibition by N-benzyloxycarbonyl-Val-Ala-asp-fluoromethylketone prevents apoptosis of lymphoma cells and loss of gag(85-93). Therefore, subversion of the epitope hierarchy in apoptotic tumor cells might be relevant in the induction of tumor-specific T-lymphocyte responses.

Castiglioni, P., Martin Fontecha, A., Milan, G., Tomajer, V., Magni, F., Michaelsson, J., et al. (2002). Apoptosis-dependent subversion of the T-lymphocyte epitope hierarchy in lymphoma cells. CANCER RESEARCH, 62(4), 1116-1122.

Apoptosis-dependent subversion of the T-lymphocyte epitope hierarchy in lymphoma cells

MAGNI, FULVIO;
2002

Abstract

Tumor cells undergoing programmed death are an attractive source of tumor-associated antigens, and evidences are available for their therapeutic efficacy in vivo when used either alone or in association with dendritic cells. However, little is known about the specificity of the immune response induced by such antigen formulation. Indeed, activation of specific proteases during apoptosis may influence the cytoplasmic degradation of proteins and the generation of CTL epitopes. We show here that on injection of C57BL/6 mice either with RMA lymphoma cells induced to apoptosis or bone marrow-derived dendritic cells pulsed with apoptotic RMA cells, a specific and protective CTL response is induced, which, however, is not directed against the immunodominant CTL epitope gag(85-93). Lack of in vivo expansion of gag(85-93)-specific CTL in vaccinated mice is attributable to the apoptosis-dependent loss of gag(85-93) in dying tumor cells. Indeed, we found loss of gag(85-93) in RMA, MBL-2, and EL-4G+ lymphoma cells, which share gag(85-93) as an immunodominant CTL epitope, induced to apoptosis by UV irradiation, mitomycin C, doxorubicin, or daunorubicin. This phenomenon appears to be caspase-dependent, because caspase inhibition by N-benzyloxycarbonyl-Val-Ala-asp-fluoromethylketone prevents apoptosis of lymphoma cells and loss of gag(85-93). Therefore, subversion of the epitope hierarchy in apoptotic tumor cells might be relevant in the induction of tumor-specific T-lymphocyte responses.
Articolo in rivista - Articolo scientifico
Thymoma; Immunodominant Epitopes; Caspases; Rauscher Virus; Lymphoma; Lymphocyte Activation; Female; Animals; T-Lymphocytes, Cytotoxic; Gene Products, gag; Epitopes, T-Lymphocyte; Apoptosis; Mice; Cancer Vaccines; Mice, Inbred C57BL
English
2002
62
4
1116
1122
none
Castiglioni, P., Martin Fontecha, A., Milan, G., Tomajer, V., Magni, F., Michaelsson, J., et al. (2002). Apoptosis-dependent subversion of the T-lymphocyte epitope hierarchy in lymphoma cells. CANCER RESEARCH, 62(4), 1116-1122.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/16231
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