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The antigenic landscape of multiple myeloma: mass spectrometry (re)defines targets for T-cell-based immunotherapy

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The antigenic landscape of multiple myeloma: mass spectrometry (re)defines targets for T-cell-based immunotherapy. / Walz, Simon; Stickel, Juliane S; Kowalewski, Daniel Johannes; Schuster, Heiko; Weisel, Katja; Backert, Linus; Kahn, Stefan; Nelde, Annika; Stroh, Tatjana; Handel, Martin; Kohlbacher, Oliver; Kanz, Lothar; Salih, Helmut Rainer; Rammensee, Hans-Georg; Stevanović, Stefan.

In: BLOOD, Vol. 126, No. 10, 03.09.2015, p. 1203-13.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Walz, S, Stickel, JS, Kowalewski, DJ, Schuster, H, Weisel, K, Backert, L, Kahn, S, Nelde, A, Stroh, T, Handel, M, Kohlbacher, O, Kanz, L, Salih, HR, Rammensee, H-G & Stevanović, S 2015, 'The antigenic landscape of multiple myeloma: mass spectrometry (re)defines targets for T-cell-based immunotherapy', BLOOD, vol. 126, no. 10, pp. 1203-13. https://doi.org/10.1182/blood-2015-04-640532

APA

Walz, S., Stickel, J. S., Kowalewski, D. J., Schuster, H., Weisel, K., Backert, L., Kahn, S., Nelde, A., Stroh, T., Handel, M., Kohlbacher, O., Kanz, L., Salih, H. R., Rammensee, H-G., & Stevanović, S. (2015). The antigenic landscape of multiple myeloma: mass spectrometry (re)defines targets for T-cell-based immunotherapy. BLOOD, 126(10), 1203-13. https://doi.org/10.1182/blood-2015-04-640532

Vancouver

Walz S, Stickel JS, Kowalewski DJ, Schuster H, Weisel K, Backert L et al. The antigenic landscape of multiple myeloma: mass spectrometry (re)defines targets for T-cell-based immunotherapy. BLOOD. 2015 Sep 3;126(10):1203-13. https://doi.org/10.1182/blood-2015-04-640532

Bibtex

@article{3e55eabe92554f00989adf0ee95cfcb5,
title = "The antigenic landscape of multiple myeloma: mass spectrometry (re)defines targets for T-cell-based immunotherapy",
abstract = "Direct analysis of HLA-presented antigens by mass spectrometry provides a comprehensive view on the antigenic landscape of different tissues/malignancies and enables the identification of novel, pathophysiologically relevant T-cell epitopes. Here, we present a systematic and comparative study of the HLA class I and II presented, nonmutant antigenome of multiple myeloma (MM). Quantification of HLA surface expression revealed elevated HLA molecule counts on malignant plasma cells compared with normal B cells, excluding relevant HLA downregulation in MM. Analyzing the presentation of established myeloma-associated T-cell antigens on the HLA ligandome level, we found a substantial proportion of antigens to be only infrequently presented on primary myelomas or to display suboptimal degrees of myeloma specificity. However, unsupervised analysis of our extensive HLA ligand data set delineated a panel of 58 highly specific myeloma-associated antigens (including multiple myeloma SET domain containing protein) which are characterized by frequent and exclusive presentation on myeloma samples. Functional characterization of these target antigens revealed peptide-specific, preexisting CD8(+) T-cell responses exclusively in myeloma patients, which is indicative of pathophysiological relevance. Furthermore, in vitro priming experiments revealed that peptide-specific T-cell responses can be induced in response-naive myeloma patients. Together, our results serve to guide antigen selection for T-cell-based immunotherapy of MM. ",
keywords = "Adult, Aged, Antigen Presentation, Antigens, Neoplasm, CD8-Positive T-Lymphocytes, Epitopes, T-Lymphocyte, Female, Histocompatibility Antigens Class I, Histocompatibility Antigens Class II, Humans, Immunotherapy, Lymphocyte Activation, Male, Middle Aged, Multiple Myeloma, Tandem Mass Spectrometry, Journal Article, Research Support, Non-U.S. Gov't",
author = "Simon Walz and Stickel, {Juliane S} and Kowalewski, {Daniel Johannes} and Heiko Schuster and Katja Weisel and Linus Backert and Stefan Kahn and Annika Nelde and Tatjana Stroh and Martin Handel and Oliver Kohlbacher and Lothar Kanz and Salih, {Helmut Rainer} and Hans-Georg Rammensee and Stefan Stevanovi{\'c}",
note = "{\textcopyright} 2015 by The American Society of Hematology.",
year = "2015",
month = sep,
day = "3",
doi = "10.1182/blood-2015-04-640532",
language = "English",
volume = "126",
pages = "1203--13",
journal = "BLOOD",
issn = "0006-4971",
publisher = "American Society of Hematology",
number = "10",

}

RIS

TY - JOUR

T1 - The antigenic landscape of multiple myeloma: mass spectrometry (re)defines targets for T-cell-based immunotherapy

AU - Walz, Simon

AU - Stickel, Juliane S

AU - Kowalewski, Daniel Johannes

AU - Schuster, Heiko

AU - Weisel, Katja

AU - Backert, Linus

AU - Kahn, Stefan

AU - Nelde, Annika

AU - Stroh, Tatjana

AU - Handel, Martin

AU - Kohlbacher, Oliver

AU - Kanz, Lothar

AU - Salih, Helmut Rainer

AU - Rammensee, Hans-Georg

AU - Stevanović, Stefan

N1 - © 2015 by The American Society of Hematology.

PY - 2015/9/3

Y1 - 2015/9/3

N2 - Direct analysis of HLA-presented antigens by mass spectrometry provides a comprehensive view on the antigenic landscape of different tissues/malignancies and enables the identification of novel, pathophysiologically relevant T-cell epitopes. Here, we present a systematic and comparative study of the HLA class I and II presented, nonmutant antigenome of multiple myeloma (MM). Quantification of HLA surface expression revealed elevated HLA molecule counts on malignant plasma cells compared with normal B cells, excluding relevant HLA downregulation in MM. Analyzing the presentation of established myeloma-associated T-cell antigens on the HLA ligandome level, we found a substantial proportion of antigens to be only infrequently presented on primary myelomas or to display suboptimal degrees of myeloma specificity. However, unsupervised analysis of our extensive HLA ligand data set delineated a panel of 58 highly specific myeloma-associated antigens (including multiple myeloma SET domain containing protein) which are characterized by frequent and exclusive presentation on myeloma samples. Functional characterization of these target antigens revealed peptide-specific, preexisting CD8(+) T-cell responses exclusively in myeloma patients, which is indicative of pathophysiological relevance. Furthermore, in vitro priming experiments revealed that peptide-specific T-cell responses can be induced in response-naive myeloma patients. Together, our results serve to guide antigen selection for T-cell-based immunotherapy of MM.

AB - Direct analysis of HLA-presented antigens by mass spectrometry provides a comprehensive view on the antigenic landscape of different tissues/malignancies and enables the identification of novel, pathophysiologically relevant T-cell epitopes. Here, we present a systematic and comparative study of the HLA class I and II presented, nonmutant antigenome of multiple myeloma (MM). Quantification of HLA surface expression revealed elevated HLA molecule counts on malignant plasma cells compared with normal B cells, excluding relevant HLA downregulation in MM. Analyzing the presentation of established myeloma-associated T-cell antigens on the HLA ligandome level, we found a substantial proportion of antigens to be only infrequently presented on primary myelomas or to display suboptimal degrees of myeloma specificity. However, unsupervised analysis of our extensive HLA ligand data set delineated a panel of 58 highly specific myeloma-associated antigens (including multiple myeloma SET domain containing protein) which are characterized by frequent and exclusive presentation on myeloma samples. Functional characterization of these target antigens revealed peptide-specific, preexisting CD8(+) T-cell responses exclusively in myeloma patients, which is indicative of pathophysiological relevance. Furthermore, in vitro priming experiments revealed that peptide-specific T-cell responses can be induced in response-naive myeloma patients. Together, our results serve to guide antigen selection for T-cell-based immunotherapy of MM.

KW - Adult

KW - Aged

KW - Antigen Presentation

KW - Antigens, Neoplasm

KW - CD8-Positive T-Lymphocytes

KW - Epitopes, T-Lymphocyte

KW - Female

KW - Histocompatibility Antigens Class I

KW - Histocompatibility Antigens Class II

KW - Humans

KW - Immunotherapy

KW - Lymphocyte Activation

KW - Male

KW - Middle Aged

KW - Multiple Myeloma

KW - Tandem Mass Spectrometry

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1182/blood-2015-04-640532

DO - 10.1182/blood-2015-04-640532

M3 - SCORING: Journal article

C2 - 26138685

VL - 126

SP - 1203

EP - 1213

JO - BLOOD

JF - BLOOD

SN - 0006-4971

IS - 10

ER -