Identification of tumor antigens among the HLA peptidomes of glioblastoma tumors and plasma Bracha Shraibman, Eilon Barnea, Dganit Melamed Kadosh, Yael Haimovich, Gleb Slobodin, Itzhak Rosner, Carlos López-Larrea, Norbert Hilf, Sabrina Kuttruff, Colette Song, Cedrik Britten, John Castle, Sebastian Kreiter, Katrin Frenzel, Marcos Tatagiba, Ghazaleh Tabatabai, Pierre-Yves Dietrich, Valérie Dutoit, Wolfgang Wick, Michael Platten, Frank Winkler, Andreas von Deimling, Judith Kroep, Juan Sahuquillo, Francisco Martinez-Ricarte, Jordi Rodon, Ulrik Lassen, Christian Ottensmeier, Sjoerd H. van der Burg, Per Thor Straten, Hans Skovgaard Poulsen, Berta Ponsati, Hideho Okada, Hans-Georg Rammensee, Ugur Sahin, Harpreet Singh and Arie Admon
| Erscheinungsform: | Aufsatz |
| Autor/Urheber: | |
| Beteiligte: | - Barnea, Eilon
- Kadosh, Dganit Melamed
- Haimovich, Yael
- Slobodin, Gleb
- Rosner, Itzhak
- López-Larrea, Carlos
- Hilf, Norbert
- Kuttruff, Sabrina
- Song, Colette
- Britten, Cedrik
- Castle, John
- Kreiter, Sebastian
- Frenzel, Katrin
- Tatagiba, Marcos
- Tabatabai, Ghazaleh
- Dietrich, Pierre-Yves
- Dutoit, Valérie
- Wick, Wolfgang
- Platten, Michael
- Winkler, Frank
- Deimling, Andreas von
- Kroep, Judith
- Sahuquillo, Juan
- Martinez-Ricarte, Francisco
- Rodon, Jordi
- Lassen, Ulrik
- Ottensmeier, Christian
- Burg, Sjoerd H. van der
- Straten, Per Thor
- Poulsen, Hans Skovgaard
- Ponsati, Berta
- Okada, Hideho
- Rammensee, Hans-Georg
- Sahin, Ugur
- Singh, Harpreet
- Admon, Arie
|
| Umfang: | 14 |
| Anmerkungen: | Gesehen am 04.02.2020 |
| Identifikatoren/Sonstige Nummern: | 1689247258 [PPN] |
| In: | Bethesda, Md. : The American Society for Biochemistry and Molecular Biology, 2002 18(2019), 6, Seite 1255-1268 volume:18 year:2019 number:6 pages:1255-1268 extent:14 |
| Inhalt: | - Graphical Abstract - <img class="highwire-fragment fragment-image" alt="Figure1" src="https://www.mcponline.org/content/mcprot/18/6/1255/F1.medium.gif" width="440" height="319"/>Download figureOpen in new tabDownload powerpoint - - Highlights - The plasma-soluble HLA peptidome of Glioblastoma contains many tumor antigens.This sHLA peptidome may serve as a rich source for disease biomarkers.The sHLA peptidomes are highly correlated with the tumor's membranal HLA peptidomes.The HLA peptidomes differ significantly from the proteomes of the tumors. - Glioblastoma multiforme (GBM) is the most aggressive brain tumor with poor prognosis to most patients. Immunotherapy of GBM is a potentially beneficial treatment option, whose optimal implementation may depend on familiarity with tumor specific antigens, presented as HLA peptides by the GBM cells. Further, early detection of GBM, such as by a routine blood test, may improve survival, even with the current treatment modalities. This study includes large-scale analyses of the HLA peptidome (immunopeptidome) of the plasma-soluble HLA molecules (sHLA) of 142 plasma samples, and the membranal HLA of GBM tumors of 10 of these patients' tumor samples. Tumor samples were fresh-frozen immediately after surgery and the plasma samples were collected before, and at multiple visits after surgery. In total, this HLA peptidome analysis involved 52 different HLA allotypes and resulted in the identification of more than 35,000 different HLA peptides. Strong correlations were observed in the signal intensities and in the repertoires of identified peptides between the tumors and plasma-soluble HLA peptidomes of the individual patients, whereas low correlations were observed between these HLA peptidomes and the tumors' proteomes. HLA peptides derived from Cancer/Testis Antigens (CTAs) were selected based on their presence among the HLA peptidomes of the patients and absence of expression of their source genes from any healthy and essential human tissues, except from immune-privileged sites. Additionally, peptides were selected as potential biomarkers if their levels in the plasma-sHLA peptidome were significantly reduced after the removal of tumor mass. The CTAs identified among the analyzed HLA peptidomes provide new opportunities for personalized immunotherapy and for early diagnosis of GBM.
|
| URL: | https://doi.org/10.1074/mcp.RA119.001524 |
| Weiter im Partnersystem: | https://swb.bsz-bw.de/DB=2.1/PPNSET?PPN=1689247258 |
leobw