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Neoantigen-reactive...
Neoantigen-reactive CD8+ T cells affect clinical outcome of adoptive cell therapy with tumor-infiltrating lymphocytes in melanoma
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- Kristensen, Nikolaj Pagh (författare)
- Technical University of Denmark
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- Heeke, Christina (författare)
- Technical University of Denmark
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- Tvingsholm, Siri A. (författare)
- Technical University of Denmark
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- Borch, Annie (författare)
- Technical University of Denmark
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- Draghi, Arianna (författare)
- Copenhagen University Hospital
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- Crowther, Michael D. (författare)
- Copenhagen University Hospital
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- Carri, Ibel (författare)
- National University of General San Martín
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- Munk, Kamilla K. (författare)
- Technical University of Denmark
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- Holm, Jeppe Sejerø (författare)
- Technical University of Denmark
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- Bjerregaard, Anne Mette (författare)
- Technical University of Denmark
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- Bentzen, Amalie Kai (författare)
- Technical University of Denmark
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- Marquard, Andrea M. (författare)
- Technical University of Denmark
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- Szallasi, Zoltan (författare)
- Danish Cancer Society
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- McGranahan, Nicholas (författare)
- University College London
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- Andersen, Rikke (författare)
- Copenhagen University Hospital
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- Nielsen, Morten (författare)
- Technical University of Denmark,National University of General San Martín
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- Jönsson, Göran B. (författare)
- Lund University,Lunds universitet,Lunds Melanomstudiegrupp,Forskargrupper vid Lunds universitet,Melanoma Genomics,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Melanom,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Lund Melanoma Study Group,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments,Melanoma,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine
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- Donia, Marco (författare)
- Copenhagen University Hospital
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- Svane, Inge Marie (författare)
- Copenhagen University Hospital
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- Hadrup, Sine Reker (författare)
- Technical University of Denmark
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(creator_code:org_t)
- 2022
- 2022
- Engelska.
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Ingår i: Journal of Clinical Investigation. - 0021-9738. ; 132:2
- Relaterad länk:
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http://dx.doi.org/10... (free)
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- BACKGROUND. Neoantigen-driven recognition and T cell–mediated killing contribute to tumor clearance following adoptive cell therapy (ACT) with tumor-infiltrating lymphocytes (TILs). Yet how diversity, frequency, and persistence of expanded neoepitope-specific CD8+ T cells derived from TIL infusion products affect patient outcome is not fully determined. METHODS. Using barcoded pMHC multimers, we provide a comprehensive mapping of CD8+ T cells recognizing neoepitopes in TIL infusion products and blood samples from 26 metastatic melanoma patients who received ACT. RESULTS. We identified 106 neoepitopes within TIL infusion products corresponding to 1.8% of all predicted neoepitopes. We observed neoepitope-specific recognition to be virtually devoid in TIL infusion products given to patients with progressive disease outcome. Moreover, we found that the frequency of neoepitope-specific CD8+ T cells in TIL infusion products correlated with increased survival and that neoepitope-specific CD8+ T cells shared with the infusion product in posttreatment blood samples were unique to responders of TIL-ACT. Finally, we found that a transcriptional signature for lymphocyte activity within the tumor microenvironment was associated with a higher frequency of neoepitope-specific CD8+ T cells in the infusion product. CONCLUSIONS. These data support previous case studies of neoepitope-specific CD8+ T cells in melanoma and indicate that successful TIL-ACT is associated with an expansion of neoepitope-specific CD8+ T cells. FUNDING. NEYE Foundation; European Research Council; Lundbeck Foundation Fellowship; Carlsberg Foundation.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
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Kristensen, Niko ...
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Heeke, Christina
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Tvingsholm, Siri ...
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Borch, Annie
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Draghi, Arianna
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Crowther, Michae ...
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visa fler...
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Carri, Ibel
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Munk, Kamilla K.
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Holm, Jeppe Seje ...
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Bjerregaard, Ann ...
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Bentzen, Amalie ...
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Marquard, Andrea ...
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Szallasi, Zoltan
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McGranahan, Nich ...
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Andersen, Rikke
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Nielsen, Morten
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Jönsson, Göran B ...
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Donia, Marco
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Svane, Inge Mari ...
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Hadrup, Sine Rek ...
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