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000125294 0247_ $$2ISSN$$a1432-0533
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000125294 1001_ $$aRapp, Carmen$$b0
000125294 245__ $$aIdentification of T cell target antigens in glioblastoma stem-like cells using an integrated proteomics-based approach in patient specimens.
000125294 260__ $$aBerlin$$bSpringer$$c2017
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000125294 520__ $$aGlioblastoma (GBM) is a highly aggressive brain tumor and still remains incurable. Among others, an immature subpopulation of self-renewing and therapy-resistant tumor cells-often referred to as glioblastoma stem-like cells (GSCs)-has been shown to contribute to disease recurrence. To target these cells personalized immunotherapy has gained a lot of interest, e.g. by reactivating pre-existing anti-tumor immune responses against GSC antigens. To identify T cell targets commonly presented by GSCs and their differentiated counterpart, we used a proteomics-based separation of GSC proteins in combination with a T cell activation assay. Altogether, 713 proteins were identified by LC-ESI-MS/MS mass spectrometry. After a thorough filtering process, 32 proteins were chosen for further analyses. Immunogenicity of corresponding peptides was tested ex vivo. A considerable number of these antigens induced T cell responses in GBM patients but not in healthy donors. Moreover, most of them were overexpressed in primary GBM and also highly expressed in recurrent GBM tissues. Interestingly, expression of the most frequent T cell target antigens could also be confirmed in quiescent, slow-cycling GSCs isolated in high purity by the DEPArray technology. Finally, for a subset of these T cell target antigens, an association between expression levels and higher T cell infiltration as well as an increased expression of positive immune modulators was observed. In summary, we identified novel immunogenic proteins, which frequently induce tumor-specific T cell responses in GBM patients and were also detected in vitro in therapy-resistant quiescent, slow-cycling GSCs. Stable expression of these T cell targets in primary and recurrent GBM support their suitability for future clinical use.
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000125294 7001_ $$aWarta, Rolf$$b1
000125294 7001_ $$0P:(DE-He78)235f4ea9af5ffa6912ebaffe647fe9b2$$aStamova, Slava$$b2
000125294 7001_ $$0P:(DE-He78)d783d5964ac0b6c9243982e6a8d1f780$$aNowrouzi, Ali$$b3
000125294 7001_ $$aGeisenberger, Christoph$$b4
000125294 7001_ $$aGal, Zoltan$$b5
000125294 7001_ $$aRoesch, Saskia$$b6
000125294 7001_ $$aDettling, Steffen$$b7
000125294 7001_ $$0P:(DE-HGF)0$$aJuenger, Simone$$b8
000125294 7001_ $$0P:(DE-He78)b832a068e7f3a70219ae501cc7a1bae6$$aBucur, Mariana$$b9
000125294 7001_ $$0P:(DE-HGF)0$$aJungk, Christine$$b10
000125294 7001_ $$aDaoTrong, Philip$$b11
000125294 7001_ $$aAhmadi, Rezvan$$b12
000125294 7001_ $$0P:(DE-He78)a1f4b408b9155beb2a8f7cba4d04fe88$$aSahm, Felix$$b13
000125294 7001_ $$0P:(DE-HGF)0$$aReuss, David$$b14
000125294 7001_ $$aFermi, Valentina$$b15
000125294 7001_ $$aHerpel, Esther$$b16
000125294 7001_ $$aEckstein, Volker$$b17
000125294 7001_ $$aGrabe, Niels$$b18
000125294 7001_ $$aSchramm, Christoph$$b19
000125294 7001_ $$aWeigand, Markus A$$b20
000125294 7001_ $$0P:(DE-He78)8714da4e45acfa36ce87c291443a9218$$aDebus, Jürgen$$b21
000125294 7001_ $$0P:(DE-He78)a8a10626a848d31e70cfd96a133cc144$$avon Deimling, Andreas$$b22
000125294 7001_ $$aUnterberg, Andreas$$b23
000125294 7001_ $$0P:(DE-He78)360c5bc2b71a849e35aca747c041dda7$$aAbdollahi, Amir$$b24$$eLast author
000125294 7001_ $$0P:(DE-He78)1732377f6242a18280bc6aaa196988d1$$aBeckhove, Philipp$$b25$$eLast author
000125294 7001_ $$0P:(DE-He78)c146c0b611b8fb654444ec078766f5ea$$aHerold-Mende, Christel$$b26
000125294 773__ $$0PERI:(DE-600)1458410-4$$a10.1007/s00401-017-1702-1$$gVol. 134, no. 2, p. 297 - 316$$n2$$p297 - 316$$tActa neuropathologica$$v134$$x1432-0533$$y2017
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