High Immunogenicity of the Human Leukocyte Antigen Peptidomes of Melanoma Tumor Cells

Jarmalavicius, Saulius; Welte, Yvonne; Walden, Peter

doi:10.1074/jbc.m112.358903

Cited by 27 publications

(33 citation statements)

References 27 publications

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“…The heterogeneity and individualization was slightly higher for the HLA-I-bound peptides than for the source proteins, as the number of shared source proteins was slightly higher compared with those of the HLA-I peptides. This has been observed also in other human cell lines and tumor samples such as melanoma (37,38,40) and depicts differences in the Ag processing and presentation in the two MUTZ3 DC differentiation states and THPMF.…”

Section: Discussionsupporting

confidence: 65%

“…First, the source proteins were derived from almost all subcellular locations, with the nucleus, cytoplasm, plasma membrane, and endoplasmic reticulum the most dominant (Fig. 5), which is similar for the HLA-I peptidome of melanoma tumor samples reported earlier (37,38), but different for other human samples such as the B lymphoblastoid cell line, where no source proteins from plasma membrane were found (39), and multiple sclerosis autopsy samples, where cytoplasm and plasma membrane were the most dominant, 34 and 24%, respectively (40). Second, the source proteins were involved in various molecular functions but especially in cell communication/signal transduction, protein metabolism, and transcription factor activity/regulator activity, and the proportion of source proteins per molecular function was similar.…”

Section: Discussionsupporting

confidence: 57%

“…The dominance of nanopeptides was also observed in the shared peptides between MUTZ3 iDC and MUTZ3 mDC, and in the HLA-A*02:01-bound peptides shared among the MUTZ3 DCs and THP1MF. This dominance of nanopeptides has also been observed in other cell lines and patient tumor samples (37)(38)(39)(40), and indicates that nine amino acids is the optimum length for MHC I-binding peptides. Decapeptides were the second most dominant and constituted 22 and 25% for MUTZ3 iDC and MUTZ3 mDC and 12% for THP1.…”

Section: Mhc I-bound Peptide Lengthssupporting

confidence: 60%

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Diverse HLA-I Peptide Repertoires of the APC Lines MUTZ3-Derived Immature and Mature Dendritic Cells and THP1-Derived Macrophages

Nyambura

Jarmalavicius

Baleeiro

et al. 2016

The Journal of Immunology

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Dendritic cells (DCs) and macrophages are specialized APCs that process and present self-Ags for induction of tolerance and foreign Ags to initiate T cell–mediated immunity. Related to differentiation states they have specific phenotypes and functions. However, the impact of these differentiations on Ag processing and presentation remains poorly defined. To gain insight into this, we analyzed and compared the HLA-I peptidomes of MUTZ3-derived human immature and mature DC lines and THP1-derived macrophages by liquid chromatography tandem mass spectrometry. We found that the HLA-I peptidomes were heterogeneous and individualized and were dominated by nonapeptides with similar HLA-I binding affinities and anchor residues. MUTZ3-derived DCs and THP1-derived macrophages were able to sample peptides from source proteins of almost all subcellular locations and were involved in various cellular functions in similar proportion, with preference to proteins involved in cell communication, signal transduction, protein metabolism, and transcription factor/regulator activity.

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Section: Discussionsupporting

confidence: 65%

Section: Discussionsupporting

confidence: 57%

Section: Mhc I-bound Peptide Lengthssupporting

confidence: 60%

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Diverse HLA-I Peptide Repertoires of the APC Lines MUTZ3-Derived Immature and Mature Dendritic Cells and THP1-Derived Macrophages

Nyambura

Jarmalavicius

Baleeiro

et al. 2016

The Journal of Immunology

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“…Four such cell lines from patients were used for MHCbound peptidome profiling [52]. After two-dimensional HPLC of eluted peptides, the authors used MALDI-TOF MS with post-source decay fragmentation as well as Q-TOF detector to analyze peptides offline and online with chromatography, correspondingly.…”

mentioning

confidence: 99%

“…Some of the epitopes identified by both methods were confirmed as immunogenic in T-cell assay. However, nucleic acid information for the proteomic search was not customized [52] and, therefore, possibly not all the neoepitopes would be identified, if any.…”

mentioning

confidence: 99%

Proteogenomics meets cancer immunology: mass spectrometric discovery and analysis of neoantigens

Polyakova

Kuznetsova

Moshkovskii³

2015

Expert Review of Proteomics

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Cancer proteogenomics is an emerging field that aims to identify and quantify protein sequence changes associated with the cancer genome. Besides being involved in cancer development and progression, such protein variants may serve as neoantigens, which provide the T-cell response against tumors. Mass spectrometry-based proteogenomics may be a promising tool for finding neoantigens in individual specimens. It is partly based on a technical background accumulated from mass spectrometric studies of peptide ligands of major histocompatibility complex proteins. Examples of the use of mass spectrometry in neoantigen identification are reviewed in this article. Some experimental workflows are discussed, which may use shotgun and targeted proteomics for translational human studies of neoepitopes, such as cancer vaccine development and checkpoint therapy response prediction.

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Argyrin F Treatment‐Induced Vulnerabilities Lead to a Novel Combination Therapy in Experimental Glioma

Walter

Canjuga

Yüz

et al. 2021

Advanced Therapeutics

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Glioblastoma are incurable primary tumors of the central nervous system that frequently harbor molecular alterations in the retinoblastoma pathway with subsequent cell cycle abnormalities. It is aimed to investigate the anti‐glioma activity of the novel cell cycle‐stabilizing compound Argyrin F and its potential treatment‐induced vulnerabilities to exploit possibilities for novel rational combination therapies. Human and murine glioma cells are used, cytotoxicity and clonogenic survival assays, cell cycle analyses, and immunoblots are performed. Residual freshly resected tissue is used for a preclinical glioma model ex vivo, i.e., patient‐derived microtumors (PDMs) for co‐culture experiments with autologous tumor‐infiltrating lymphocytes (TILs). Mass spectrometry‐based immunopeptidomics are performed and the orthotopic syngeneic SMA560/VM/Dk glioma mouse model is used. Argyrin F‐induced cell cycle arrest and reduced clonogenic survival is observed. Argyrin F‐treated experimental glioma in vivo displays 4.6‐fold more glioma‐infiltrating CD8+ T cells. A distinctive treatment‐induced immunopeptidome is discovered. The combination of Argyrin F plus PD‐1 antibody increases cellular toxicity in PDM/TILs co‐cultures ex vivo and prolonged overall survival compared with monotherapies in vivo. Thus, Argyrin F leads to anti‐glioma effects and increases the immunogenicity, paving the way for a novel combination therapy of Argyrin F plus PD‐1 blockade.

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High Immunogenicity of the Human Leukocyte Antigen Peptidomes of Melanoma Tumor Cells

Cited by 27 publications

References 27 publications

Diverse HLA-I Peptide Repertoires of the APC Lines MUTZ3-Derived Immature and Mature Dendritic Cells and THP1-Derived Macrophages

Diverse HLA-I Peptide Repertoires of the APC Lines MUTZ3-Derived Immature and Mature Dendritic Cells and THP1-Derived Macrophages

Proteogenomics meets cancer immunology: mass spectrometric discovery and analysis of neoantigens

Argyrin F Treatment‐Induced Vulnerabilities Lead to a Novel Combination Therapy in Experimental Glioma

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