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Acquired immune res...
Acquired immune resistance follows complete tumor regression without loss of target antigens or IFNγ signaling
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- Donia, Marco (author)
- Copenhagen University Hospital,University of Copenhagen
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- Harbst, Katja (author)
- Lund University,Lunds universitet,Lunds Melanomstudiegrupp,Forskargrupper vid Lunds universitet,Melanoma Genomics,Lund Melanoma Study Group,Lund University Research Groups
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- van Buuren, Marit M (author)
- Neon Therapeutics,Netherlands Cancer Institute
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- Kvistborg, Pia (author)
- Netherlands Cancer Institute
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- Lindberg, Mattias F. (author)
- University of Gothenburg
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- Andersen, Rikke Dorothea (author)
- Copenhagen University Hospital
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- Idorn, Manja (author)
- Copenhagen University Hospital
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- Ahmad, Shamaila Munir (author)
- Copenhagen University Hospital
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- Ellebæk, Eva (author)
- Copenhagen University Hospital
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- Mueller, Anja (author)
- Martin-Luther-Universität Halle-Wittenberg
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- Fagone, Paolo (author)
- University of Catania
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- Nicoletti, Ferdinando (author)
- University of Catania
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- Libra, Massimo (author)
- University of Catania
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- Lauss, Martin (author)
- Lund 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
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- Hadrup, Sine Reker (author)
- Technical University of Denmark,Copenhagen University Hospital
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- Schmidt, Henrik (author)
- Aarhus University Hospital
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- Andersen, Mads Hald (author)
- Copenhagen University Hospital
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- Thor Straten, Per (author)
- Copenhagen University Hospital
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- Nilsson, Jonas (author)
- Netherlands Cancer Institute
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- Schumacher, Ton N (author)
- University of Gothenburg
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- Seliger, Barbara (author)
- Martin-Luther-Universität Halle-Wittenberg
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- Jönsson, Göran (author)
- Lund 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
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- Svane, Inge Marie (author)
- Copenhagen University Hospital
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(creator_code:org_t)
- 2017
- 2017
- English 5 s.
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In: Cancer Research. - 0008-5472. ; 77:17, s. 4562-4566
- Related links:
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http://dx.doi.org/10...
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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Abstract
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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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Publication and Content Type
- art (subject category)
- ref (subject category)
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- By the author/editor
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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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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Cancer and Oncol ...
- Articles in the publication
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Cancer Research
- By the university
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Lund University