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Mutational and putative neoantigen load predict clinical benefit of adoptive T cell therapy in melanoma

Lauss, Martin LU ; Donia, Marco; Harbst, Katja LU ; Andersen, Rikke; Mitra, Shamik LU ; Rosengren, Frida LU ; Salim, Maryem LU ; Vallon-Christersson, Johan LU ; Törngren, Therese LU and Kvist, Anders LU , et al. (2017) In Nature Communications 8(1).
Abstract

Adoptive T-cell therapy (ACT) is a highly intensive immunotherapy regime that has yielded remarkable response rates and many durable responses in clinical trials in melanoma; however, 50-60% of the patients have no clinical benefit. Here, we searched for predictive biomarkers to ACT in melanoma. Whole exome-and transcriptome sequencing and neoantigen prediction were applied to pre-treatment samples from 27 patients recruited to a clinical phase I/II trial of ACT in stage IV melanoma. All patients had previously progressed on other immunotherapies. We report that clinical benefit is associated with significantly higher predicted neoantigen load. High mutation and predicted neoantigen load are significantly associated with improved... (More)

Adoptive T-cell therapy (ACT) is a highly intensive immunotherapy regime that has yielded remarkable response rates and many durable responses in clinical trials in melanoma; however, 50-60% of the patients have no clinical benefit. Here, we searched for predictive biomarkers to ACT in melanoma. Whole exome-and transcriptome sequencing and neoantigen prediction were applied to pre-treatment samples from 27 patients recruited to a clinical phase I/II trial of ACT in stage IV melanoma. All patients had previously progressed on other immunotherapies. We report that clinical benefit is associated with significantly higher predicted neoantigen load. High mutation and predicted neoantigen load are significantly associated with improved progression-free and overall survival. Further, clinical benefit is associated with the expression of immune activation signatures including a high MHC-I antigen processing and presentation score. These results improve our understanding of mechanisms behind clinical benefit of ACT in melanoma.

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Nature Communications
volume
8
issue
1
publisher
Nature Publishing Group
external identifiers
  • scopus:85035025088
  • wos:000416229300024
ISSN
2041-1723
DOI
10.1038/s41467-017-01460-0
language
English
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yes
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169352f6-c6fb-4343-8c90-187e2e18fbc5
date added to LUP
2017-12-07 13:56:30
date last changed
2018-01-16 13:27:04
@article{169352f6-c6fb-4343-8c90-187e2e18fbc5,
  abstract     = {<p>Adoptive T-cell therapy (ACT) is a highly intensive immunotherapy regime that has yielded remarkable response rates and many durable responses in clinical trials in melanoma; however, 50-60% of the patients have no clinical benefit. Here, we searched for predictive biomarkers to ACT in melanoma. Whole exome-and transcriptome sequencing and neoantigen prediction were applied to pre-treatment samples from 27 patients recruited to a clinical phase I/II trial of ACT in stage IV melanoma. All patients had previously progressed on other immunotherapies. We report that clinical benefit is associated with significantly higher predicted neoantigen load. High mutation and predicted neoantigen load are significantly associated with improved progression-free and overall survival. Further, clinical benefit is associated with the expression of immune activation signatures including a high MHC-I antigen processing and presentation score. These results improve our understanding of mechanisms behind clinical benefit of ACT in melanoma.</p>},
  articleno    = {1738},
  author       = {Lauss, Martin and Donia, Marco and Harbst, Katja and Andersen, Rikke and Mitra, Shamik and Rosengren, Frida and Salim, Maryem and Vallon-Christersson, Johan and Törngren, Therese and Kvist, Anders and Ringnér, Markus and Svane, Inge Marie and Jönsson, Göran},
  issn         = {2041-1723},
  language     = {eng},
  month        = {12},
  number       = {1},
  publisher    = {Nature Publishing Group},
  series       = {Nature Communications},
  title        = {Mutational and putative neoantigen load predict clinical benefit of adoptive T cell therapy in melanoma},
  url          = {http://dx.doi.org/10.1038/s41467-017-01460-0},
  volume       = {8},
  year         = {2017},
}