000292117 001__ 292117 000292117 005__ 20250228163922.0 000292117 0247_ $$2doi$$a10.1016/j.mcpro.2024.100825 000292117 0247_ $$2pmid$$apmid:39111711 000292117 0247_ $$2ISSN$$a1535-9476 000292117 0247_ $$2ISSN$$a1535-9484 000292117 0247_ $$2altmetric$$aaltmetric:166018317 000292117 037__ $$aDKFZ-2024-01616 000292117 041__ $$aEnglish 000292117 082__ $$a610 000292117 1001_ $$0P:(DE-He78)154b320ef9a6e95f0081a85ef24eb3a3$$aSalek, Mogjiborahman$$b0$$eFirst author 000292117 245__ $$aoptiPRM: A targeted immunopeptidomics LC-MS workflow with ultra-high sensitivity for the detection of mutation-derived tumor neoepitopes from limited input material. 000292117 260__ $$aBethesda, Md.$$bThe American Society for Biochemistry and Molecular Biology$$c2024 000292117 3367_ $$2DRIVER$$aarticle 000292117 3367_ $$2DataCite$$aOutput Types/Journal article 000292117 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1740749185_28369 000292117 3367_ $$2BibTeX$$aARTICLE 000292117 3367_ $$2ORCID$$aJOURNAL_ARTICLE 000292117 3367_ $$00$$2EndNote$$aJournal Article 000292117 500__ $$a#EA:D410#LA:D410# / HI-TRON / 2024, 23(9), art. no. 100825 000292117 520__ $$aPersonalized cancer immunotherapies such as therapeutic vaccines and adoptive transfer of T cell receptor (TCR)-transgenic T cells rely on the presentation of tumor-specific peptides by human leukocyte antigen (HLA) class I molecules to cytotoxic T cells. Such neoepitopes can for example arise from somatic mutations and their identification is crucial for the rational design of new therapeutic interventions. Liquid chromatography mass spectrometry (LC-MS)-based immunopeptidomics is the only method to directly prove actual peptide presentation and we have developed a parameter optimization workflow to tune targeted assays for maximum detection sensitivity on a per peptide basis, termed optiPRM. Optimization of collision energy using optiPRM allows for improved detection of low abundant peptides that are very hard to detect using standard parameters. Applying this to immunopeptidomics, we detected a neoepitope in a patient-derived xenograft (PDX) from as little as 2.5×106 cells input. Application of the workflow on small patient tumor samples allowed for the detection of five mutation-derived neoepitopes in three patients. One neoepitope was confirmed to be recognized by patient T cells. In conclusion, optiPRM, a targeted MS workflow reaching ultra-high sensitivity by per peptide parameter optimization, which makes the identification of actionable neoepitopes possible from sample sizes usually available in the clinic. 000292117 536__ $$0G:(DE-HGF)POF4-314$$a314 - Immunologie und Krebs (POF4-314)$$cPOF4-314$$fPOF IV$$x0 000292117 588__ $$aDataset connected to CrossRef, PubMed, , Journals: inrepo02.dkfz.de 000292117 7001_ $$0P:(DE-He78)1dfe5fa05989d8b5eeb8bd098e2f1c1f$$aFörster, Jonas$$b1$$eFirst author$$udkfz 000292117 7001_ $$0P:(DE-He78)45aa4fa7b16296bd3454cc3b68c33fc1$$aBecker, Jonas$$b2$$eFirst author$$udkfz 000292117 7001_ $$0P:(DE-He78)27b8b96bde8e36bbbc5e91485b08411a$$aMeyer, Marten$$b3$$udkfz 000292117 7001_ $$0P:(DE-He78)8dde8d3920dc06c59314abdb4ac7d2e8$$aCharoentong, Pornpimol$$b4$$udkfz 000292117 7001_ $$0P:(DE-He78)558f7ddc9b9893d0f57eb74e243cc4fd$$aLyu, Yanhong$$b5$$udkfz 000292117 7001_ $$0P:(DE-He78)9c599f876c762bc78d289674c15ba4a5$$aLindner, 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