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Immunopeptides presented by HLA class I initiate immunogenicity, and mass spectrometry enables identification of naturally processed and presented neoantigen candidates. Multiomics expansion, improved MS sensitivity, and deep/machine-learning peptide search algorithms are strengthening immunopeptidomics, which this review surveys with a focus on future directions for cancer immunotherapy.",{"@graph":14,"@context":73},[15,34,56],{"@type":16,"itemListElement":17},"BreadcrumbList",[18,23,27,31],{"item":19,"name":20,"@type":21,"position":22},"https://docshare.wps.com","Home","ListItem",1,{"item":24,"name":25,"@type":21,"position":26},"https://docshare.wps.com/document/","Document",2,{"item":28,"name":29,"@type":21,"position":30},"https://docshare.wps.com/document/research-report/","Research & 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immunopeptidomics for neoantigen discovery?",{"text":72,"@type":64},"Mass spectrometry can select naturally processed and actually presented TSA candidates, helping researchers obtain a comprehensive view of the immunopeptidome.","https://schema.org",{"og:url":32,"og:type":75,"og:title":10,"og:site_name":45,"og:description":12},"article",{"robots":77,"canonical":32},"index,follow",{"doc_id":79,"site_id":7},330410,1790927329,{"code":4,"msg":82,"data":83},"success",[84,88,92,96,101,106,111,115,120,123,127],{"id":22,"doc_module":4,"doc_module_name":25,"category_name":85,"show_sort_weight":86,"slug":87},"Story & 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10. 1111/cas.16118  \nR E V I E W A RT I C L E  \nEmerging potential of immunopeptidomics by mass spectrometry in cancer immunotherapy  \nYuriko Minegishi  | Yoshimi Haga  | Koji Ueda   \nCancer Proteomics Group, Cancer Precision Medicine Center, Japanese Foundation for Cancer Research, Tokyo, Japan  \nCorrespondence  \nYuriko Minegishi, Cancer Proteomics Group, Cancer Precision Medicine Center, Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, Tokyo 135-8550, Japan.  \n[Email:](Email: yuriko.minegishi@jfcr.or.jp)[ yuriko.minegishi@jfcr.or.jp](Email: yuriko.minegishi@jfcr.or.jp)  \nFunding information  \nJapan Agency for Medical Research and Development, Grant/Award Number: 20ae0101074s0302; Shimadzu Corporation; Japan Society for the Promotion of Science, Grant/Award Number: 23K04971  \nAbstract  \nWith significant advances in analytical technologies, research in the field of cancer immunotherapy, such as adoptive T cell therapy, cancer vaccine, and immune checkpoint blockade (ICB), is currently gaining tremendous momentum. Since the efficacy of cancer immunotherapy is recognized only by a minority of patients, more potent tumor-specific antigens (TSAs, also known as neoantigens) and predictive markers for treatment response are of great interest. In cancer immunity, immunopeptides, presented by human leukocyte antigen (HLA) class I, play a role as initiating mediators of immunogenicity. The latest advancement in the interdisciplinary multiomics approach has rapidly enlightened us about the identity of the “dark matter” of cancer and the associated immunopeptides. In this field, mass spectrometry (MS) is a viable option to select because of the naturally processed and actually presented TSA candidates in order to grasp the whole picture of the immunopeptidome. In the past few years the search space has been enlarged by the multiomics approach, the sensitivity of mass spectrometers has been improved, and deep/machine-learning-supported peptide search algorithms have taken immunopeptidomics to the next level. In this review, along with the introduction of key technical advancements in immunopeptidomics, the potential and further directions of immunopeptidomics will be reviewed from the perspective of cancer immunotherapy.  \nK E Y WO R D S  \ncancer immunotherapy, immunopeptidomics, mass spectrometry, neoantigen  \n1 | INTRODUCTION  \nMass spectrometry (MS) is an analytical instrument that can obtain an over view of proteins (proteome), peptides (peptidome), and binding partner analysis (interactome) against the target of interest.1 In  \nrecent years, MS analysis has been significantly improved through synergies with advances in deep sequencing and deep learning technologies (Figure 1) . Together with the development of the latest mass spectrometers and peripheral devices, the file size of raw data obtained by MS analysis is now greater than ever before. One  \nAbbreviations: DDA, data-dependent acquisition; DIA, data-independent acquisition; DIM, differential ion mobility; HLA, human leukocyte antigen; ICB, immune checkpoint blockade; IM, ion mobility; MRM, multiple-reaction monitoring; MS, mass spectrometry; NCP, noncanonical ORF-derived protein; ORF, open reading frame; PDC, patient-derived cell; PRM, parallel reaction monitoring; PTM, post-translational modification; Ribo-seq, ribosomal sequencing; RNA-seq, RNA sequencing; TIM, trapped ion mobility; tMS2, targeted MS2; TSA, tumor-specific antigen; WES, whole-exome sequencing.  \nThis is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.  \n© 2024 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.  \nresearch subject that has largely ","cbCaiaSyhultOFy1","https://ap.wps.com/l/cbCaiaSyhultOFy1","pdf",4080262,12,"English","# Abstract\n# Keywords\n# Introduction\n## Immunopeptides and HLA presentation\n## Mass spectrometry in immunopeptidomics\n## Challenges in neoantigen prediction","[{\"question\":\"Why are tumor-specific antigens and predictive markers important in cancer immunotherapy?\",\"answer\":\"Cancer immunotherapy efficacy is recognized only in a minority of patients, so stronger tumor-specific antigens and markers that can predict treatment response are of high interest.\"},{\"question\":\"What role do immunopeptides play in cancer immunity?\",\"answer\":\"Immunopeptides presented by HLA class I function as initiating mediators of immunogenicity, linking antigen presentation to immune activation.\"},{\"question\":\"How does mass spectrometry support immunopeptidomics for neoantigen discovery?\",\"answer\":\"Mass spectrometry can select naturally processed and actually presented TSA candidates, helping researchers obtain a comprehensive view of the immunopeptidome.\"}]","Emerging potential of immunopeptidomics by mass spectrometry in cancer immunotherapy | PDF",1789988726]