Identification of T cell target antigens in glioblastoma stem-like cells using an integrated proteomics-based approach in patient specimens

AbstractGlioblastoma (GBM) is a highly aggressive brain tumor and still remains incurable. Among others, an immature subpopulation of self-renewing and therapy-resistant tumor cells —often referred to as glioblastoma stem-like cells (GSCs)—has been shown to contribute to disease recurrence. To target these cells personalized immunotherapy has gained a lot of interest, e.g. by reactivating pre-existing anti-tumor immune responses against GSC antigens. To identify T cell targ ets commonly presented by GSCs and their differentiated counterpart, we used a proteomics-based separation of GSC proteins in combination with a T cell activation assay. Altogether, 713 proteins were identified by LC–ESI–MS/MS mass spectrometry. After a thorough filtering process, 32 proteins we re chosen for further analyses. Immunogenicity of corresponding peptides was tested ex vivo. A considerable number of these antigens induced T cell responses in GBM patients but not in healthy donors. Moreover, most of them were overexpressed in primary GBM and also highly expressed in recurrent GB M tissues. Interestingly, expression of the most frequent T cell target antigens could also be confirmed in quiescent, slow-cycling GSCs isolated in high purity by the DEPArray technology. Finally, for a subset of these T cell target antigens, an association between expression levels and higher T c ell infiltration as well as an increased expression of positive immune modulators was observed. In summary, we ide...
Source: Acta Neuropathologica - Category: Neurology Source Type: research