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Mapping the HLA Ligandome of Colorectal Cancer Reveals an Imprint of Malignant Cell Transformation

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Mapping the HLA Ligandome of Colorectal Cancer Reveals an Imprint of Malignant Cell Transformation. / Löffler, Markus W; Kowalewski, Daniel J; Backert, Linus; Bernhardt, Jörg; Adam, Patrick; Schuster, Heiko; Dengler, Florian; Backes, Daniel; Kopp, Hans-Georg; Beckert, Stefan; Wagner, Silvia; Königsrainer, Ingmar; Kohlbacher, Oliver; Kanz, Lothar; Königsrainer, Alfred; Rammensee, Hans-Georg; Stevanović, Stefan; Haen, Sebastian P.

In: CANCER RES, Vol. 78, No. 16, 15.08.2018, p. 4627-4641.

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

Harvard

Löffler, MW, Kowalewski, DJ, Backert, L, Bernhardt, J, Adam, P, Schuster, H, Dengler, F, Backes, D, Kopp, H-G, Beckert, S, Wagner, S, Königsrainer, I, Kohlbacher, O, Kanz, L, Königsrainer, A, Rammensee, H-G, Stevanović, S & Haen, SP 2018, 'Mapping the HLA Ligandome of Colorectal Cancer Reveals an Imprint of Malignant Cell Transformation', CANCER RES, vol. 78, no. 16, pp. 4627-4641. https://doi.org/10.1158/0008-5472.CAN-17-1745

APA

Löffler, M. W., Kowalewski, D. J., Backert, L., Bernhardt, J., Adam, P., Schuster, H., Dengler, F., Backes, D., Kopp, H-G., Beckert, S., Wagner, S., Königsrainer, I., Kohlbacher, O., Kanz, L., Königsrainer, A., Rammensee, H-G., Stevanović, S., & Haen, S. P. (2018). Mapping the HLA Ligandome of Colorectal Cancer Reveals an Imprint of Malignant Cell Transformation. CANCER RES, 78(16), 4627-4641. https://doi.org/10.1158/0008-5472.CAN-17-1745

Vancouver

Löffler MW, Kowalewski DJ, Backert L, Bernhardt J, Adam P, Schuster H et al. Mapping the HLA Ligandome of Colorectal Cancer Reveals an Imprint of Malignant Cell Transformation. CANCER RES. 2018 Aug 15;78(16):4627-4641. https://doi.org/10.1158/0008-5472.CAN-17-1745

Bibtex

@article{ab7e75a7bb2d40ce98877200cea109a4,
title = "Mapping the HLA Ligandome of Colorectal Cancer Reveals an Imprint of Malignant Cell Transformation",
abstract = "Immune cell infiltrates have proven highly relevant for colorectal carcinoma prognosis, making colorectal cancer a promising candidate for immunotherapy. Because tumors interact with the immune system via HLA-presented peptide ligands, exact knowledge of the peptidome constitution is fundamental for understanding this relationship. Here, we comprehensively describe the naturally presented HLA ligandome of colorectal carcinoma and corresponding nonmalignant colon (NMC) tissue. Mass spectrometry identified 35,367 and 28,132 HLA class I ligands on colorectal carcinoma and NMC, attributable to 7,684 and 6,312 distinct source proteins, respectively. Cancer-exclusive peptides were assessed on source protein level using the Kyoto Encyclopedia of Genes and Genomes (KEGG) and protein analysis through evolutionary relationships (PANTHER), revealing pathognomonic colorectal carcinoma-associated pathways, including Wnt, TGFβ, PI3K, p53, and RTK-RAS. Relative quantitation of peptide presentation on paired colorectal carcinoma and NMC tissue further identified source proteins from cancer- and infection-associated pathways to be overrepresented merely within the colorectal carcinoma ligandome. From the pool of tumor-exclusive peptides, a selected HLA-ligand subset was assessed for immunogenicity, with the majority exhibiting an existing T-cell repertoire. Overall, these data show that the HLA ligandome reflects cancer-associated pathways implicated in colorectal carcinoma oncogenesis, suggesting that alterations in tumor cell metabolism could result in cancer-specific, albeit not mutation-derived, tumor antigens. Hence, a defined pool of unique tumor peptides, attributable to complex cellular alterations that are exclusive to malignant cells, might comprise promising candidates for immunotherapeutic applications.Significance: Cancer-associated pathways are reflected in the antigenic landscape of colorectal cancer, suggesting that tumor-specific antigens do not necessarily have to be mutation-derived but may also originate from other alterations in cancer cells. Cancer Res; 78(16); 4627-41. {\textcopyright}2018 AACR.",
keywords = "Amino Acid Sequence/genetics, Antigen Presentation/immunology, Antigens, Neoplasm/genetics, Cell Transformation, Neoplastic/genetics, Colorectal Neoplasms/genetics, HLA Antigens/genetics, Humans, Immunotherapy, Ligands, Mass Spectrometry, Peptides/genetics, T-Lymphocytes/immunology",
author = "L{\"o}ffler, {Markus W} and Kowalewski, {Daniel J} and Linus Backert and J{\"o}rg Bernhardt and Patrick Adam and Heiko Schuster and Florian Dengler and Daniel Backes and Hans-Georg Kopp and Stefan Beckert and Silvia Wagner and Ingmar K{\"o}nigsrainer and Oliver Kohlbacher and Lothar Kanz and Alfred K{\"o}nigsrainer and Hans-Georg Rammensee and Stefan Stevanovi{\'c} and Haen, {Sebastian P}",
note = "{\textcopyright}2018 American Association for Cancer Research.",
year = "2018",
month = aug,
day = "15",
doi = "10.1158/0008-5472.CAN-17-1745",
language = "English",
volume = "78",
pages = "4627--4641",
journal = "CANCER RES",
issn = "0008-5472",
publisher = "American Association for Cancer Research Inc.",
number = "16",

}

RIS

TY - JOUR

T1 - Mapping the HLA Ligandome of Colorectal Cancer Reveals an Imprint of Malignant Cell Transformation

AU - Löffler, Markus W

AU - Kowalewski, Daniel J

AU - Backert, Linus

AU - Bernhardt, Jörg

AU - Adam, Patrick

AU - Schuster, Heiko

AU - Dengler, Florian

AU - Backes, Daniel

AU - Kopp, Hans-Georg

AU - Beckert, Stefan

AU - Wagner, Silvia

AU - Königsrainer, Ingmar

AU - Kohlbacher, Oliver

AU - Kanz, Lothar

AU - Königsrainer, Alfred

AU - Rammensee, Hans-Georg

AU - Stevanović, Stefan

AU - Haen, Sebastian P

N1 - ©2018 American Association for Cancer Research.

PY - 2018/8/15

Y1 - 2018/8/15

N2 - Immune cell infiltrates have proven highly relevant for colorectal carcinoma prognosis, making colorectal cancer a promising candidate for immunotherapy. Because tumors interact with the immune system via HLA-presented peptide ligands, exact knowledge of the peptidome constitution is fundamental for understanding this relationship. Here, we comprehensively describe the naturally presented HLA ligandome of colorectal carcinoma and corresponding nonmalignant colon (NMC) tissue. Mass spectrometry identified 35,367 and 28,132 HLA class I ligands on colorectal carcinoma and NMC, attributable to 7,684 and 6,312 distinct source proteins, respectively. Cancer-exclusive peptides were assessed on source protein level using the Kyoto Encyclopedia of Genes and Genomes (KEGG) and protein analysis through evolutionary relationships (PANTHER), revealing pathognomonic colorectal carcinoma-associated pathways, including Wnt, TGFβ, PI3K, p53, and RTK-RAS. Relative quantitation of peptide presentation on paired colorectal carcinoma and NMC tissue further identified source proteins from cancer- and infection-associated pathways to be overrepresented merely within the colorectal carcinoma ligandome. From the pool of tumor-exclusive peptides, a selected HLA-ligand subset was assessed for immunogenicity, with the majority exhibiting an existing T-cell repertoire. Overall, these data show that the HLA ligandome reflects cancer-associated pathways implicated in colorectal carcinoma oncogenesis, suggesting that alterations in tumor cell metabolism could result in cancer-specific, albeit not mutation-derived, tumor antigens. Hence, a defined pool of unique tumor peptides, attributable to complex cellular alterations that are exclusive to malignant cells, might comprise promising candidates for immunotherapeutic applications.Significance: Cancer-associated pathways are reflected in the antigenic landscape of colorectal cancer, suggesting that tumor-specific antigens do not necessarily have to be mutation-derived but may also originate from other alterations in cancer cells. Cancer Res; 78(16); 4627-41. ©2018 AACR.

AB - Immune cell infiltrates have proven highly relevant for colorectal carcinoma prognosis, making colorectal cancer a promising candidate for immunotherapy. Because tumors interact with the immune system via HLA-presented peptide ligands, exact knowledge of the peptidome constitution is fundamental for understanding this relationship. Here, we comprehensively describe the naturally presented HLA ligandome of colorectal carcinoma and corresponding nonmalignant colon (NMC) tissue. Mass spectrometry identified 35,367 and 28,132 HLA class I ligands on colorectal carcinoma and NMC, attributable to 7,684 and 6,312 distinct source proteins, respectively. Cancer-exclusive peptides were assessed on source protein level using the Kyoto Encyclopedia of Genes and Genomes (KEGG) and protein analysis through evolutionary relationships (PANTHER), revealing pathognomonic colorectal carcinoma-associated pathways, including Wnt, TGFβ, PI3K, p53, and RTK-RAS. Relative quantitation of peptide presentation on paired colorectal carcinoma and NMC tissue further identified source proteins from cancer- and infection-associated pathways to be overrepresented merely within the colorectal carcinoma ligandome. From the pool of tumor-exclusive peptides, a selected HLA-ligand subset was assessed for immunogenicity, with the majority exhibiting an existing T-cell repertoire. Overall, these data show that the HLA ligandome reflects cancer-associated pathways implicated in colorectal carcinoma oncogenesis, suggesting that alterations in tumor cell metabolism could result in cancer-specific, albeit not mutation-derived, tumor antigens. Hence, a defined pool of unique tumor peptides, attributable to complex cellular alterations that are exclusive to malignant cells, might comprise promising candidates for immunotherapeutic applications.Significance: Cancer-associated pathways are reflected in the antigenic landscape of colorectal cancer, suggesting that tumor-specific antigens do not necessarily have to be mutation-derived but may also originate from other alterations in cancer cells. Cancer Res; 78(16); 4627-41. ©2018 AACR.

KW - Amino Acid Sequence/genetics

KW - Antigen Presentation/immunology

KW - Antigens, Neoplasm/genetics

KW - Cell Transformation, Neoplastic/genetics

KW - Colorectal Neoplasms/genetics

KW - HLA Antigens/genetics

KW - Humans

KW - Immunotherapy

KW - Ligands

KW - Mass Spectrometry

KW - Peptides/genetics

KW - T-Lymphocytes/immunology

U2 - 10.1158/0008-5472.CAN-17-1745

DO - 10.1158/0008-5472.CAN-17-1745

M3 - SCORING: Journal article

C2 - 29789417

VL - 78

SP - 4627

EP - 4641

JO - CANCER RES

JF - CANCER RES

SN - 0008-5472

IS - 16

ER -