PMID- 29658117 OWN - NLM STAT- MEDLINE DCOM- 20190529 LR - 20211204 IS - 1365-2567 (Electronic) IS - 0019-2805 (Print) IS - 0019-2805 (Linking) VI - 154 IP - 3 DP - 2018 Jul TI - Mapping the tumour human leukocyte antigen (HLA) ligandome by mass spectrometry. PG - 331-345 LID - 10.1111/imm.12936 [doi] AB - The entirety of human leukocyte antigen (HLA)-presented peptides is referred to as the HLA ligandome of a cell or tissue, in tumours often termed immunopeptidome. Mapping the tumour immunopeptidome by mass spectrometry (MS) comprehensively views the pathophysiologically relevant antigenic signature of human malignancies. MS is an unbiased approach stringently filtering the candidates to be tested as opposed to epitope prediction algorithms. In the setting of peptide-specific immunotherapies, MS-based strategies significantly diminish the risk of lacking clinical benefit, as they yield highly enriched amounts of truly presented peptides. Early immunopeptidomic efforts were severely limited by technical sensitivity and manual spectra interpretation. The technological progress with development of orbitrap mass analysers and enhanced chromatographic performance led to vast improvements in mass accuracy, sensitivity, resolution, and speed. Concomitantly, bioinformatic tools were developed to process MS data, integrate sequencing results, and deconvolute multi-allelic datasets. This enabled the immense advancement of tumour immunopeptidomics. Studying the HLA-presented peptide repertoire bears high potential for both answering basic scientific questions and translational application. Mapping the tumour HLA ligandome has started to significantly contribute to target identification for the design of peptide-specific cancer immunotherapies in clinical trials and compassionate need treatments. In contrast to prediction algorithms, rare HLA allotypes and HLA class II can be adequately addressed when choosing MS-guided target identification platforms. Herein, we review the identification of tumour HLA ligands focusing on sources, methods, bioinformatic data analysis, translational application, and provide an outlook on future developments. CI - (c) 2018 John Wiley & Sons Ltd. FAU - Freudenmann, Lena Katharina AU - Freudenmann LK AUID- ORCID: 0000-0002-9827-4979 AD - Interfaculty Institute for Cell Biology, Department of Immunology, University of Tubingen, Tubingen, Germany. AD - DKFZ Partner Site Tubingen, German Cancer Consortium (DKTK), Tubingen, Germany. FAU - Marcu, Ana AU - Marcu A AUID- ORCID: 0000-0003-0808-8097 AD - Interfaculty Institute for Cell Biology, Department of Immunology, University of Tubingen, Tubingen, Germany. FAU - Stevanovic, Stefan AU - Stevanovic S AUID- ORCID: 0000-0003-1954-7762 AD - Interfaculty Institute for Cell Biology, Department of Immunology, University of Tubingen, Tubingen, Germany. AD - DKFZ Partner Site Tubingen, German Cancer Consortium (DKTK), Tubingen, Germany. LA - eng PT - Journal Article PT - Review DEP - 20180508 PL - England TA - Immunology JT - Immunology JID - 0374672 RN - 0 (Antigens, Neoplasm) RN - 0 (Epitopes) RN - 0 (HLA Antigens) RN - 0 (Ligands) RN - 0 (Peptides) SB - IM MH - Animals MH - Antigens, Neoplasm/chemistry/immunology/metabolism MH - Computational Biology/methods MH - *Epitope Mapping/methods MH - Epitopes/*immunology/isolation & purification/metabolism MH - HLA Antigens/*immunology/metabolism MH - Humans MH - Immunotherapy MH - *Ligands MH - *Mass Spectrometry/methods MH - Neoplasms/*immunology/metabolism/therapy MH - Peptides/chemistry/immunology/metabolism MH - Precision Medicine/methods MH - Protein Processing, Post-Translational MH - Translational Research, Biomedical PMC - PMC6002237 OTO - NOTNLM OT - HLA ligand OT - TAA OT - cancer immunotherapy OT - immunopeptidome OT - mass spectrometry OT - tumour-associated antigen EDAT- 2018/04/17 06:00 MHDA- 2019/05/30 06:00 PMCR- 2019/07/01 CRDT- 2018/04/17 06:00 PHST- 2018/03/02 00:00 [received] PHST- 2018/03/29 00:00 [revised] PHST- 2018/04/02 00:00 [accepted] PHST- 2018/04/17 06:00 [pubmed] PHST- 2019/05/30 06:00 [medline] PHST- 2018/04/17 06:00 [entrez] PHST- 2019/07/01 00:00 [pmc-release] AID - IMM12936 [pii] AID - 10.1111/imm.12936 [doi] PST - ppublish SO - Immunology. 2018 Jul;154(3):331-345. doi: 10.1111/imm.12936. Epub 2018 May 8.