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

Martin Lauss, Marco Donia, Katja Harbst, Rikke Andersen, Shamik Mitra, Frida Rosengren, Maryem Salim, Johan Vallon-Christersson, Therese Törngren, Anders Kvist, Markus Ringnér, Inge Marie Svane and Göran Jönsson
Additional contact information
Martin Lauss: Lund University
Marco Donia: Department of Hematology
Katja Harbst: Lund University
Rikke Andersen: Department of Hematology
Shamik Mitra: Lund University
Frida Rosengren: Lund University
Maryem Salim: Lund University
Johan Vallon-Christersson: Lund University
Therese Törngren: Lund University
Anders Kvist: Lund University
Markus Ringnér: Lund University
Inge Marie Svane: Department of Hematology
Göran Jönsson: Lund University

Nature Communications, 2017, vol. 8, issue 1, 1-11

Abstract: 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 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.

Date: 2017
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DOI: 10.1038/s41467-017-01460-0

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