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

Institut for Klinisk Medicin

12 Citationer (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.

Originalsprog	Engelsk
Tidsskrift	Molecular and Cellular Proteomics
Vol/bind	17
Udgave nummer	11
Sider (fra-til)	2132-2145
Antal sider	14
ISSN	1535-9476
DOI	https://doi.org/10.1074/mcp.ra118.000792
Status	Udgivet - nov. 2018

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10.1074/mcp.ra118.000792Licens: CC BY

http://europepmc.org/articles/pmc6210219?pdf=render

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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, bind 17, nr. 11, s. 2132-2145. https://doi.org/10.1074/mcp.ra118.000792

@article{a76c30d123b94f699ac3c07b9e107b41,

title = "Identification of Tumor Antigens Among the HLA Peptidomes of Glioblastoma Tumors and Plasma",

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.",

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",

author = "Bracha Shraibman and Eilon Barnea and Kadosh, {Dganit Melamed} and Yael Haimovich and Gleb Slobodin and Itzhak Rosner and Carlos L{\'o}pez-Larrea and Norbert Hilf and Sabrina Kuttruff and Colette Song and Cedrik Britten and John Castle and Sebastian Kreiter and Katrin Frenzel and Marcos Tatagiba and Ghazaleh Tabatabai and Pierre-Yves Dietrich and Val{\'e}rie Dutoit and Wolfgang Wick and Michael Platten and Frank Winkler and {von Deimling}, Andreas and Judith Kroep and Juan Sahuquillo and Francisco Martinez-Ricarte and Jordi Rodon and Ulrik Lassen and Christian Ottensmeier and {van der Burg}, {Sjoerd H} and {Thor Straten}, Per and Poulsen, {Hans Skovgaard} and Berta Ponsati and Hideho Okada and Hans-Georg Rammensee and Ugur Sahin and Harpreet Singh and Arie Admon",

year = "2018",

month = nov,

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

language = "English",

volume = "17",

pages = "2132--2145",

journal = "Molecular and Cellular Proteomics",

issn = "1535-9476",

publisher = "American Society for Biochemistry and Molecular Biology",

number = "11",

}

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

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

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