Immunological evaluation of a novel HLA-A2 restricted phosphopeptide of tumor associated Antigen, TRAP1, on cancer therapy

Lin, Min-Han; Shen, Kuan-Yin; Liu, Bing-Sin; Chen, I-Hua; Sher, Yuh‐Pyng; Tseng, Guan-Chin; Liu, Shih‐Jen; Sung, Wang-Chou

doi:10.1016/j.jvacx.2019.100017

Cited by 15 publications

(17 citation statements)

References 45 publications

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“…Several studies reported that phosphorylated peptides could induce immune responses through T cell recognition. For instance, T cells were shown to recognize phosphorylated peptides presented on primary tumors and normal tissues and kill tumor cell lines (26,31). Studies have reported a clear preference for the phosphorylation at position 4 on HLA-I ligands and revealed an increased presence of arginine at P1 as well as an enrichment of proline after the phosphosite caused by proline-dependent kinases (20, 21, 24, 26-30, 32, 33).…”

Section: Introductionmentioning

confidence: 99%

Mass spectrometry based immunopeptidomics leads to robust predictions of phosphorylated HLA class I ligands

Solleder

Guillaume

Racle

et al. 2019

Preprint

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Declaration of Interest:The authors declare no potential conflicts of interest. AbstractThe presentation of peptides on class I human leukocyte antigen (HLA-I) molecules plays a central role in immune recognition of infected or malignant cells. In cancer, non-self HLA-I ligands can arise from many different alterations, including non-synonymous mutations, gene fusion, cancer-specific alternative mRNA splicing or aberrant post-translational modifications. Identifying HLA-I ligands remains a challenging task that requires either heavy experimental work for in-vivo identification or optimized bioinformatics tools for accurate predictions. To date, no HLA-I ligand predictor includes post-translational modifications. To fill this gap, we curated phosphorylated HLA-I ligands from several immunopeptidomics studies (including six newly measured samples) covering 72 HLA-I alleles, and retrieved a total of 2,066 unique phosphorylated peptides. We then expanded our motif deconvolution tool to identify precise binding motifs of phosphorylated HLA-I ligands.Our results reveal a clear enrichment of phosphorylated peptides among HLA-C ligands and demonstrate a prevalent role of both HLA-I motifs and kinase motifs on the presentation of phosphorylated peptides. This data further enabled us to develop and validate the first predictor of interactions between HLA-I molecules and phosphorylated peptides.

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Section: Introductionmentioning

confidence: 99%

Mass spectrometry based immunopeptidomics leads to robust predictions of phosphorylated HLA class I ligands

Solleder

Guillaume

Racle

et al. 2019

Preprint

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“…On an antigenic level, phosphorylated proteins were shown to be processed normally by the antigen presentation pathway of both normal and tumoral cells (146)(147)(148)(149)(150)(151)(152). In line with the idea that they could be used for immunotherapies, several studies reported that phosphorylated peptides, but not their dephosphorylated counterparts, could activate T cells in the mice model (150,153). Although their immunogenic potential has not been demonstrated in human, attempts are currently being made to integrate peptide phosphorylation into MHC I binding prediction tools (154).…”

Section: Tumor-specific Antigen Derived From Post-translation Modificmentioning

confidence: 99%

A Roadmap Toward the Definition of Actionable Tumor-Specific Antigens

2020

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The search for tumor-specific antigens (TSAs) has considerably accelerated during the past decade due to the improvement of proteogenomic detection methods. This provides new opportunities for the development of novel antitumoral immunotherapies to mount an efficient T cell response against one or multiple types of tumors. While the identification of mutated antigens originating from coding exons has provided relatively few TSA candidates, the possibility of enlarging the repertoire of targetable TSAs by looking at antigens arising from non-canonical open reading frames opens up interesting avenues for cancer immunotherapy. In this review, we outline the potential sources of TSAs and the mechanisms responsible for their expression strictly in cancer cells. In line with the heterogeneity of cancer, we propose that discrete families of TSAs may be enriched in specific cancer types.

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“…PTMs like phosphorylation were shown to be deregulated in cancer cells, causing aberrant cellular behavior (Krueger and Srivastava, 2006; López-Otín and Hunter, 2010; Martín-Bernabé et al, 2017). Therefore, phosphorylated peptides presented on HLA molecules provide potential targets for the development of immunotherapeutic strategies (Engelhard et al, 2020; Lin et al, 2019; Meyer et al, 2009; Petersen et al, 2009a). While many studies analyzed phosphorylated peptides presented on HLA-I molecules (Alpízar et al, 2017; Andersen et al, 1999; Cobbold et al, 2013; Mohammed et al, 2008; Petersen et al, 2009b; Solleder et al, 2020; Zarling et al, 2006), phosphorylated HLA-II ligands have received much less attention.…”

Section: Introductionmentioning

confidence: 99%

Deciphering the landscape of phosphorylated HLA-II ligands

Solleder

Racle

Guillaume

et al. 2021

Preprint

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CD4+ T-cell activation in infectious diseases and cancer is governed by the recognition of peptides presented on class II human leukocyte antigen (HLA-II) molecules. Therefore, HLA-II ligands represent promising targets for vaccine design and personalized cancer immunotherapy. Much work has been done to identify and predict unmodified peptides presented on HLA-II molecules. However, little is known about the presentation of phosphorylated HLA-II ligands. Here, we analyzed Mass Spectrometry HLA-II peptidomics data and identified 1,113 unique phosphorylated HLA-II ligands. This enabled us to precisely define phosphorylated binding motifs for more than 30 common HLA-II alleles and to explore various molecular properties of phosphorylated peptides. Our data were further used to develop the first predictor of phosphorylated peptide presentation on HLA-II molecules.

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Immunological evaluation of a novel HLA-A2 restricted phosphopeptide of tumor associated Antigen, TRAP1, on cancer therapy

Cited by 15 publications

References 45 publications

Mass spectrometry based immunopeptidomics leads to robust predictions of phosphorylated HLA class I ligands

Mass spectrometry based immunopeptidomics leads to robust predictions of phosphorylated HLA class I ligands

A Roadmap Toward the Definition of Actionable Tumor-Specific Antigens

Deciphering the landscape of phosphorylated HLA-II ligands

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