title: HLA class I-restrictedMYD88L265P-derived peptides as specific targets for lymphoma immunotherapy.
abstract: Genome sequencing has uncovered an array of recurring somatic mutations in different non-Hodgkin lymphoma (NHL) subtypes. If affecting protein-coding regions, such mutations may yield mutation-derived peptides that may be presented by HLA class I proteins and recognized by cytotoxic T cells. A recurring somatic and oncogenic driver mutation of the Toll-like receptor adaptor proteinMYD88, Leu265Pro (L265P) was identified in up to 90% of different NHL subtype patients. We therefore screened the potential ofMYD88L265P-derived peptides to elicit cytotoxic T cell responses as tumor-specific neoantigens. Based onin silicopredictions, we identified potentialMYD88L265P-containing HLA ligands for several HLA class I restrictions. A set of HLA class IMYD88L265P-derived ligands elicited specific cytotoxic T cell responses for HLA-B*07 and -B*15. These data highlight the potential ofMYD88L265Pmutation-specific peptide-based immunotherapy as a novel personalized treatment approach for patients withMYD88L265P+NHLs that may complement pharmacological approaches targeting oncogenic MyD88 L265P signaling.
authors.affiliation: Department of Immunology, Institute for Cell Biology, University of Tübingen , Tübingen, Germany.
authors.forename: Annika
authors.initials: A
authors.lastname: Nelde
authors.affiliation: Department of Hematology and Oncology, University Hospital Tübingen , Tübingen, Germany.
authors.forename: Juliane Sarah
authors.initials: JS
authors.lastname: Walz
authors.affiliation: Department of Immunology, Institute for Cell Biology, University of Tübingen , Tübingen, Germany.
authors.forename: Daniel Johannes
authors.initials: DJ
authors.lastname: Kowalewski
authors.affiliation: Department of Immunology, Institute for Cell Biology, University of Tübingen , Tübingen, Germany.
authors.forename: Heiko
authors.initials: H
authors.lastname: Schuster
authors.affiliation: Department of Immunology, Institute for Cell Biology, University of Tübingen , Tübingen, Germany.
authors.forename: Olaf-Oliver
authors.initials: OO
authors.lastname: Wolz
authors.affiliation: Department of Immunology, Institute for Cell Biology, University of Tübingen , Tübingen, Germany.
authors.forename: Janet Kerstin
authors.initials: JK
authors.lastname: Peper
authors.affiliation: Department of Immunology, Institute for Cell Biology, University of Tübingen , Tübingen, Germany.
authors.forename: Yamel
authors.initials: Y
authors.lastname: Cardona Gloria
authors.affiliation: Department of Immunology, Erasmus MC Rotterdam , Rotterdam, the Netherlands.
authors.forename: Anton W
authors.initials: AW
authors.lastname: Langerak
authors.affiliation: Department of Immunology, Erasmus MC Rotterdam , Rotterdam, the Netherlands.
authors.forename: Alice F
authors.initials: AF
authors.lastname: Muggen
authors.affiliation: Department of Hematology, Oncology and Stem Cell Transplantation, University Medical Center Freiburg , Freiburg, Germany.
authors.forename: Rainer
authors.initials: R
authors.lastname: Claus
authors.affiliation: Department of Pathology, University Hospital Tübingen , Tübingen, Germany.
authors.forename: Irina
authors.initials: I
authors.lastname: Bonzheim
authors.affiliation: Department of Pathology, University Hospital Tübingen , Tübingen, Germany.
authors.forename: Falko
authors.initials: F
authors.lastname: Fend
authors.affiliation: Department of Hematology and Oncology, University Hospital Tübingen, Tübingen, Germany; Clinical Cooperation Unit Translational Immunology, German Cancer Consortium (DKTK), DKFZ Partner Site Tübingen, Tübingen, Germany.
authors.forename: Helmut Rainer
authors.initials: HR
authors.lastname: Salih
authors.affiliation: Department of Hematology and Oncology, University Hospital Tübingen , Tübingen, Germany.
authors.forename: Lothar
authors.initials: L
authors.lastname: Kanz
authors.affiliation: Department of Immunology, Institute for Cell Biology, University of Tübingen, Tübingen, Germany; German Cancer Consortium (DKTK), DKFZ Partner Site Tübingen, Tübingen, Germany.
authors.forename: Hans-Georg
authors.initials: HG
authors.lastname: Rammensee
authors.affiliation: Department of Immunology, Institute for Cell Biology, University of Tübingen, Tübingen, Germany; German Cancer Consortium (DKTK), DKFZ Partner Site Tübingen, Tübingen, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Stevanović
authors.affiliation: Department of Immunology, Institute for Cell Biology, University of Tübingen , Tübingen, Germany.
authors.forename: Alexander N R
authors.initials: AN
authors.lastname: Weber
keywords: Cancer vaccine; HLA ligandome; MyD88 L265P; immunotherapy; neoantigen; non-Hodgkin lymphoma; peptide vaccination