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Despite being considered as a disease with low mutational burden and thus poor immunogenic, CLL seems to retain the ability of eliciting specific T cell activation. Accordingly, we recently found non-mutated tumor-associated antigens to play a central role in CLL immunosurveillance. Here, we investigated the association of total and CLL-exclusive HLA class I and HLA class II peptide presentation in the mass spectrometry-defined immunopeptidome of leukemic cells with clinical features and disease outcome of 57 CLL patients. Patients whose CLL cells present a more diverse immunopeptidome experienced fewer relapses. During the follow-up phase of up to 10 years, patients with an HLA class I-restricted presentation of high numbers of total and CLL-exclusive peptides on their malignant cells showed a more favorable disease course with a prolonged progression-free survival (PFS). Overall, our results suggest the existence of an efficient T cell-based immunosurveillance mediated by CLL-associated tumor antigens, supporting ongoing efforts in developing T cell-based immunotherapeutic strategies for CLL.<\/jats:p>","DOI":"10.3390\/cancers14194659","type":"journal-article","created":{"date-parts":[[2022,9,25]],"date-time":"2022-09-25T21:14:28Z","timestamp":1664140468000},"page":"4659","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Immunopeptidome Diversity in Chronic Lymphocytic Leukemia Identifies Patients with Favorable Disease Outcome"],"prefix":"10.3390","volume":"14","author":[{"given":"Maddalena","family":"Marconato","sequence":"first","affiliation":[{"name":"Clinical Collaboration Unit Translational Immunology, German Cancer Consortium (DKTK), Department of Internal Medicine, University Hospital T\u00fcbingen, 72076 T\u00fcbingen, Germany"},{"name":"Cluster of Excellence iFIT (EXC2180) \u201cImage-Guided and Functionally Instructed Tumor Therapies\u201d, University of T\u00fcbingen, Auf der Morgenstelle 15, 72076 T\u00fcbingen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2197-8740","authenticated-orcid":false,"given":"Yacine","family":"Maringer","sequence":"additional","affiliation":[{"name":"Cluster of Excellence iFIT (EXC2180) \u201cImage-Guided and Functionally Instructed Tumor Therapies\u201d, University of T\u00fcbingen, Auf der Morgenstelle 15, 72076 T\u00fcbingen, Germany"},{"name":"Department of Peptide-Based Immunotherapy, University and University Hospital T\u00fcbingen, 72076 T\u00fcbingen, Germany"},{"name":"Institute for Cell Biology, Department of Immunology, University of T\u00fcbingen, 72076 T\u00fcbingen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6404-7391","authenticated-orcid":false,"given":"Juliane S.","family":"Walz","sequence":"additional","affiliation":[{"name":"Clinical Collaboration Unit Translational Immunology, German Cancer Consortium (DKTK), Department of Internal Medicine, University Hospital T\u00fcbingen, 72076 T\u00fcbingen, Germany"},{"name":"Cluster of Excellence iFIT (EXC2180) \u201cImage-Guided and Functionally Instructed Tumor Therapies\u201d, University of T\u00fcbingen, Auf der Morgenstelle 15, 72076 T\u00fcbingen, Germany"},{"name":"Department of Peptide-Based Immunotherapy, University and University Hospital T\u00fcbingen, 72076 T\u00fcbingen, Germany"},{"name":"Institute for Cell Biology, Department of Immunology, University of T\u00fcbingen, 72076 T\u00fcbingen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8504-8481","authenticated-orcid":false,"given":"Annika","family":"Nelde","sequence":"additional","affiliation":[{"name":"Cluster of Excellence iFIT (EXC2180) \u201cImage-Guided and Functionally Instructed Tumor Therapies\u201d, University of T\u00fcbingen, Auf der Morgenstelle 15, 72076 T\u00fcbingen, Germany"},{"name":"Department of Peptide-Based Immunotherapy, University and University Hospital T\u00fcbingen, 72076 T\u00fcbingen, Germany"},{"name":"Institute for Cell Biology, Department of Immunology, University of T\u00fcbingen, 72076 T\u00fcbingen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jonas S.","family":"Heitmann","sequence":"additional","affiliation":[{"name":"Clinical Collaboration Unit Translational Immunology, German Cancer Consortium (DKTK), Department of Internal Medicine, University Hospital T\u00fcbingen, 72076 T\u00fcbingen, Germany"},{"name":"Cluster of Excellence iFIT (EXC2180) \u201cImage-Guided and Functionally Instructed Tumor Therapies\u201d, University of T\u00fcbingen, Auf der Morgenstelle 15, 72076 T\u00fcbingen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1052","DOI":"10.1056\/NEJM199510193331606","article-title":"Chronic lymphocytic leukemia","volume":"333","author":"Rozman","year":"1995","journal-title":"N. 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