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; Arie Admon

doi:10.1074/mcp.ra118.000792

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 PlattenFrank 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, Arie Admon

Department of Clinical Medicine

12 Citations (Scopus)

Abstract

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. Furthermore, 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.

Original language	English
Journal	Molecular and Cellular Proteomics
Volume	17
Issue number	11
Pages (from-to)	2132-2145
Number of pages	14
ISSN	1535-9476
DOIs	https://doi.org/10.1074/mcp.ra118.000792
Publication status	Published - Nov 2018

Keywords

Alleles
Amino Acid Sequence
Antigens, Neoplasm/blood
Biomarkers, Tumor/blood
Cell Membrane/metabolism
Glioblastoma/blood
HLA Antigens/metabolism
Humans
Peptides/blood
Proteome/metabolism
Solubility

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Shraibman, B., Barnea, E., Kadosh, D. M., Haimovich, Y., Slobodin, G., Rosner, I., López-Larrea, C., Hilf, N., Kuttruff, S., Song, C., Britten, C., Castle, J., Kreiter, S., Frenzel, K., Tatagiba, M., Tabatabai, G., Dietrich, P-Y., Dutoit, V., Wick, W., ... Admon, A. (2018). Identification of Tumor Antigens Among the HLA Peptidomes of Glioblastoma Tumors and Plasma. Molecular and Cellular Proteomics, 17(11), 2132-2145. https://doi.org/10.1074/mcp.ra118.000792

Shraibman, B, Barnea, E, Kadosh, DM, Haimovich, Y, Slobodin, G, Rosner, I, López-Larrea, C, Hilf, N, Kuttruff, S, Song, C, Britten, C, Castle, J, Kreiter, S, Frenzel, K, Tatagiba, M, Tabatabai, G, Dietrich, P-Y, Dutoit, V, Wick, W, Platten, M, Winkler, F, von Deimling, A, Kroep, J, Sahuquillo, J, Martinez-Ricarte, F, Rodon, J, Lassen, U, Ottensmeier, C, van der Burg, SH, Thor Straten, P, Poulsen, HS, Ponsati, B, Okada, H, Rammensee, H-G, Sahin, U, Singh, H & Admon, A 2018, 'Identification of Tumor Antigens Among the HLA Peptidomes of Glioblastoma Tumors and Plasma', Molecular and Cellular Proteomics, vol. 17, no. 11, pp. 2132-2145. https://doi.org/10.1074/mcp.ra118.000792

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abstract = "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. Furthermore, 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.",

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doi = "10.1074/mcp.ra118.000792",

language = "English",

volume = "17",

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journal = "Molecular and Cellular Proteomics",

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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

PY - 2018/11

Y1 - 2018/11

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. Furthermore, 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. Furthermore, 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.

KW - Alleles

KW - Amino Acid Sequence

KW - Antigens, Neoplasm/blood

KW - Biomarkers, Tumor/blood

KW - Cell Membrane/metabolism

KW - Glioblastoma/blood

KW - HLA Antigens/metabolism

KW - Humans

KW - Peptides/blood

KW - Proteome/metabolism

KW - Solubility

U2 - 10.1074/mcp.ra118.000792

DO - 10.1074/mcp.ra118.000792

M3 - Journal article

C2 - 30072578

SN - 1535-9476

VL - 17

SP - 2132

EP - 2145

JO - Molecular and Cellular Proteomics

JF - Molecular and Cellular Proteomics

IS - 11

ER -

Identification of Tumor Antigens Among the HLA Peptidomes of Glioblastoma Tumors and Plasma

Abstract

Keywords

UN SDGs

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