TY - JOUR
T1 - Identification of Tumor Antigens Among the HLA Peptidomes of Glioblastoma Tumors and Plasma
AU - Shraibman, Bracha
AU - Barnea, Eilon
AU - Kadosh, Dganit Melamed
AU - Haimovich, Yael
AU - Slobodin, Gleb
AU - Rosner, Itzhak
AU - López-Larrea, Carlos
AU - Hilf, Norbert
AU - Kuttruff, Sabrina
AU - Song, Colette
AU - Britten, Cedrik
AU - Castle, John
AU - Kreiter, Sebastian
AU - Frenzel, Katrin
AU - Tatagiba, Marcos
AU - Tabatabai, Ghazaleh
AU - Dietrich, Pierre-Yves
AU - Dutoit, Valérie
AU - Wick, Wolfgang
AU - Platten, Michael
AU - Winkler, Frank
AU - von Deimling, Andreas
AU - Kroep, Judith
AU - Sahuquillo, Juan
AU - Martinez-Ricarte, Francisco
AU - Rodon, Jordi
AU - Lassen, Ulrik
AU - Ottensmeier, Christian
AU - van der Burg, Sjoerd H
AU - Thor Straten, Per
AU - Poulsen, Hans Skovgaard
AU - Ponsati, Berta
AU - Okada, Hideho
AU - Rammensee, Hans-Georg
AU - Sahin, Ugur
AU - Singh, Harpreet
AU - Admon, Arie
N1 - Withdrawn publication
PY - 2019/1/1
Y1 - 2019/1/1
N2 - 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.
AB - 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.
U2 - 10.1074/mcp.RA119.001524
DO - 10.1074/mcp.RA119.001524
M3 - Journal article
C2 - 31154438
SN - 1535-9476
VL - 18
SP - 1255
EP - 1268
JO - Molecular & cellular proteomics : MCP
JF - Molecular & cellular proteomics : MCP
IS - 6
ER -