HSP90 inhibitor 17-DMAG enhances EphA2+ tumor cell recognition by specific CD8+ T cells (40.27)
| Autor: | Mayumi Kawabe, Maja Mandic, Jennifer Taylor, Cecilia Vasquez, Amy Wesa, Leonard Neckers, Walter Storkus |
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| Rok vydání: | 2009 |
| Předmět: | |
| Zdroj: | The Journal of Immunology. 182:40.27-40.27 |
| ISSN: | 1550-6606 0022-1767 |
| Popis: | EphA2, a member of receptor tyrosine kinases (RTK), is commonly expressed by a broad range of cancer types, where its level of (over)expression correlates with poor clinical outcome. Since tumor cell expressed EphA2 is a non-mutated "self" protein, specific CD8+ T cells are subject to self-tolerance mechanisms and typically exhibit only moderate-to-low functional avidity, rendering them marginally competent to recognize EphA2+ tumor cells in vitro or in vivo. We have recently reported that the ability of specific CD8+ T cells to recognize EphA2+ tumor cells can be augmented after the cancer cells are pretreated with EphA2 agonists that promote proteasomal degradation (Wesa et al., J. Immunol., in press, 2008). In the current study we show that treatment of EphA2+ tumor cells with the HSP90 inhibitor, 17-DMAG, similarly enhances EphA2 degradation by the proteasome, minimally impairs MHC class I antigen presentign machinery, and increases tumor cell recognition by specific CD8+ T cell lines and clones in vitro. These studies suggest that EphA2 represents a novel HSP90 client protein and that the treatment of cancer patients with 17-DMAG-based "pulse" therapy may improve the anti-tumor efficacy of CD8+ T effector cells reactive against EphA2-derived epitopes. |
| Databáze: | OpenAIRE |
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