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@ARTICLE{Zaghla:307576,
      author       = {B. K. Q. Zaghla and Z. Safyürek and D. Gröger and S.
                      Mecklenbräuker and N.-S. Lingstädt and O. Popp and J.
                      Spengler and M. Haji and M. Montesion and L. A. Albacker and
                      P. Mertins and M. G. Klatt$^*$},
      title        = {{S}ystematic evaluation of neoepitope predictions
                      challenges clinically observed {T}-cell responses and their
                      impact on immune evasion.},
      journal      = {Journal for ImmunoTherapy of Cancer},
      volume       = {14},
      number       = {1},
      issn         = {2051-1426},
      address      = {London},
      publisher    = {BioMed Central},
      reportid     = {DKFZ-2026-00071},
      pages        = {e013271},
      year         = {2026},
      note         = {#DKTKZFB26#},
      abstract     = {Peptide presentation on human leukocyte antigens (HLAs) is
                      essential for initiating T-cell responses and all
                      consequences of this presentation including anticancer
                      immunity or immune escape. Many studies have relied on in
                      silico prediction tools rather than biological measurement
                      of HLA presentation to study these effects. To better assess
                      the frequency and consequences of neoantigen presentation,
                      we overexpressed 125 combinations of full-length neoantigens
                      and one HLA class I allele to experimentally validate
                      presentation of mutated and non-mutated HLA ligands through
                      HLA ligand isolation followed by tandem mass spectrometry. A
                      successful presentation was observed only in $22\%$ of
                      predicted cases with strong implications on previously
                      described downstream effects. For example, the association
                      of HLA loss of heterozygosity with predicted neoepitopes was
                      challenged for $58\%$ (73/125) of combinations. Furthermore,
                      when testing 51 sequences used for personalized messenger
                      RNA neoepitope vaccines, we observed that clinical responses
                      were independent of the presentation status of the
                      neoepitopes. Even a presumably neoepitope-specific and
                      strongly expanded T cell receptor clone from a neoantigen
                      vaccination study could not be linked to a successfully
                      presented neoepitope. Overall, these data highlight the
                      importance of validating the presentation of neoepitopes to
                      fully understand our interpretation of clinical
                      mutation-specific responses and their related effects,
                      including immune evasion.},
      keywords     = {Humans / Immune Evasion / T-Lymphocytes: immunology /
                      Epitopes, T-Lymphocyte: immunology / Antigens, Neoplasm:
                      immunology / Antigens, Neoplasm: genetics / Antigen
                      Presentation: immunology / HLA Antigens: immunology / HLA
                      Antigens: genetics / Cancer Vaccines: immunology /
                      Histocompatibility Antigens Class I: immunology /
                      Histocompatibility Antigens Class I: genetics / Human
                      leukocyte antigen - HLA (Other) / Immunotherapy (Other) / T
                      cell Receptor - TCR (Other) / Vaccine (Other) / Epitopes,
                      T-Lymphocyte (NLM Chemicals) / Antigens, Neoplasm (NLM
                      Chemicals) / HLA Antigens (NLM Chemicals) / Cancer Vaccines
                      (NLM Chemicals) / Histocompatibility Antigens Class I (NLM
                      Chemicals)},
      cin          = {BE01},
      ddc          = {610},
      cid          = {I:(DE-He78)BE01-20160331},
      pnm          = {899 - ohne Topic (POF4-899)},
      pid          = {G:(DE-HGF)POF4-899},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:41506790},
      doi          = {10.1136/jitc-2025-013271},
      url          = {https://inrepo02.dkfz.de/record/307576},
}