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

TY - JOUR

T1 - Mutational and putative neoantigen load predict clinical benefit of adoptive T cell therapy in melanoma

AU - Lauss, Martin

AU - Donia, Marco

AU - Harbst, Katja

AU - Andersen, Rikke

AU - Mitra, Shamik

AU - Rosengren, Frida

AU - Salim, Maryem

AU - Vallon-Christersson, Johan

AU - Törngren, Therese

AU - Kvist, Anders

AU - Ringnér, Markus

AU - Svane, Inge Marie

AU - Jönsson, Göran

PY - 2017

Y1 - 2017

N2 - 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.

AB - 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.

U2 - 10.1038/s41467-017-01460-0

DO - 10.1038/s41467-017-01460-0

M3 - Journal article

C2 - 29170503

AN - SCOPUS:85035025088

SN - 2041-1723

VL - 8

JO - Nature Communications

JF - Nature Communications

M1 - 1738

ER -