There are various Damage-Associated Molecular Patterns (DAMPs) that are recognizable by the immune system in the cancer microenvironment. DAMPs are revealed under a specific type of cell death termed immunogenic cell death in which stimuli force the cancer cells to die and leave antigen traces such as heat shock proteins that can be used against the disease. The stimulus of interest in this study was recombinant human Tumor-necrosis factor-related apoptosis-inducing ligand (TRAIL) which was known to selectively kill cancer cells such as glioblastoma cells. This study examined the role of TRAIL in immunogenic cell death for brain cancer. High density T98G glioblastoma cells were cultured with or without 50 ng/ml recombinant human TRAIL for four days. The trypan blue exclusion assay revealed that the average death rate for the TRAIL treated glioblastoma cells was 42%. Furthermore, western blot analysis showed that TRAIL treated cells had a reduction in heat shock protein 70 expression. Previous studies in the literature showed heat shock protein 70 mediated apoptosis resistance in cancer cells. The current study suggests that, even in the absence of any other inhibitors, heat shock protein 70 down-regulation via TRAIL may cause the chemoresistant glioblastoma cells to become susceptible to TRAIL-mediated cell death. Future studies will further investigate the relationship between DAMPs and TRAIL and the extent to which TRAIL generates sufficient apoptotic glioblastoma cells that would serve as the antigenic source for T cell immunotherapy regimens.
Disclaimer: This research was supported in part by the James A. Haley Veterans' Hospital. The contents of this publication do not represent the views of the Department of Veterans Affairs or the United States Government.
Citation Format: Andrea N. McCray. TRAIL mediated reduction of an immunogenic cell death protein, heat shock protein 70, in glioblastoma. [abstract]. In: Proceedings of the AACR Special Conference: Tumor Immunology and Immunotherapy: A New Chapter; December 1-4, 2014; Orlando, FL. Philadelphia (PA): AACR; Cancer Immunol Res 2015;3(10 Suppl):Abstract nr A28.
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