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Acquired immune res...
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Donia, MarcoCopenhagen University Hospital,University of Copenhagen
(author)
Acquired immune resistance follows complete tumor regression without loss of target antigens or IFNγ signaling
- Article/chapterEnglish2017
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LIBRIS-ID:oai:lup.lub.lu.se:95d483b6-e0e8-401a-a0d0-bf17b6061b15
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https://lup.lub.lu.se/record/95d483b6-e0e8-401a-a0d0-bf17b6061b15URI
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https://doi.org/10.1158/0008-5472.CAN-16-3172DOI
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Language:English
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Summary in:English
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Subject category:art swepub-publicationtype
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Subject category:ref swepub-contenttype
Notes
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Cancer immunotherapy can result in durable tumor regressions in some patients. However, patients who initially respond often experience tumor progression. Here, we report mechanistic evidence of tumoral immune escape in an exemplary clinical case: a patient with metastatic melanoma who developed disease recurrence following an initial, unequivocal radiologic complete regression after T-cell–based immunotherapy. Functional cytotoxic T-cell responses, including responses to one mutant neoantigen, were amplified effectively with therapy and generated durable immunologic memory. However, these immune responses, including apparently effective surveillance of the tumor mutanome, did not prevent recurrence. Alterations of the MHC class I antigen-processing and presentation machinery (APM) in resistant cancer cells, but not antigen loss or impaired IFNγ signaling, led to impaired recognition by tumor-specific CD8þ T cells. Our results suggest that future immunotherapy combinations should take into account targeting cancer cells with intact and impaired MHC class I–related APM. Loss of target antigens or impaired IFNγ signaling does not appear to be mandatory for tumor relapse after a complete radiologic regression. Personalized studies to uncover mechanisms leading to disease recurrence within each individual patient are warranted.
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Added entries (persons, corporate bodies, meetings, titles ...)
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Harbst, KatjaLund University,Lunds universitet,Lunds Melanomstudiegrupp,Forskargrupper vid Lunds universitet,Melanoma Genomics,Lund Melanoma Study Group,Lund University Research Groups(Swepub:lu)med-kbn
(author)
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van Buuren, Marit MNetherlands Cancer Institute,Neon Therapeutics
(author)
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Kvistborg, PiaNetherlands Cancer Institute
(author)
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Lindberg, Mattias F.University of Gothenburg
(author)
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Andersen, Rikke DorotheaCopenhagen University Hospital
(author)
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Idorn, ManjaCopenhagen University Hospital
(author)
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Ahmad, Shamaila MunirCopenhagen University Hospital
(author)
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Ellebæk, EvaCopenhagen University Hospital
(author)
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Mueller, AnjaMartin-Luther-Universität Halle-Wittenberg
(author)
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Fagone, PaoloUniversity of Catania
(author)
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Nicoletti, FerdinandoUniversity of Catania
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Libra, MassimoUniversity of Catania
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Lauss, MartinLund University,Lunds universitet,Bröstcancer-genetik,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Melanoma Genomics,Forskargrupper vid Lunds universitet,Breastcancer-genetics,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine,Lund University Research Groups(Swepub:lu)med-mlu
(author)
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Hadrup, Sine RekerCopenhagen University Hospital,Technical University of Denmark
(author)
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Schmidt, HenrikAarhus University Hospital
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Andersen, Mads HaldCopenhagen University Hospital
(author)
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Thor Straten, PerCopenhagen University Hospital
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Nilsson, JonasNetherlands Cancer Institute
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Schumacher, Ton NUniversity of Gothenburg
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Seliger, BarbaraMartin-Luther-Universität Halle-Wittenberg
(author)
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Jönsson, GöranLund University,Lunds universitet,Bröstcancer-genetik,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Breastcancer-genetics,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine(Swepub:lu)onk-gjo
(author)
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Svane, Inge MarieCopenhagen University Hospital
(author)
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Copenhagen University HospitalUniversity of Copenhagen
(creator_code:org_t)
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In:Cancer Research77:17, s. 4562-45660008-5472
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Donia, Marco
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Harbst, Katja
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van Buuren, Mari ...
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Kvistborg, Pia
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Lindberg, Mattia ...
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Andersen, Rikke ...
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Idorn, Manja
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Ahmad, Shamaila ...
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Ellebæk, Eva
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Mueller, Anja
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Fagone, Paolo
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Nicoletti, Ferdi ...
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Libra, Massimo
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Lauss, Martin
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Hadrup, Sine Rek ...
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Schmidt, Henrik
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Andersen, Mads H ...
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Thor Straten, Pe ...
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Nilsson, Jonas
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Schumacher, Ton ...
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Seliger, Barbara
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Jönsson, Göran
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Svane, Inge Mari ...
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Cancer Research
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Lund University