TY - JOUR
T1 - Genomic and immune heterogeneity are associated with differential responses to therapy in melanoma
AU - Reuben, Alexandre
AU - Spencer, Christine N.
AU - Prieto, Peter A.
AU - Gopalakrishnan, Vancheswaran
AU - Reddy, Sangeetha M.
AU - Miller, John P.
AU - Mao, Xizeng
AU - De Macedo, Mariana Petaccia
AU - Chen, Jiong
AU - Song, Xingzhi
AU - Jiang, Hong
AU - Chen, Pei Ling
AU - Beird, Hannah C.
AU - Garber, Haven R.
AU - Roh, Whijae
AU - Wani, Khalida
AU - Chen, Eveline
AU - Haymaker, Cara
AU - Forget, Marie Andrée
AU - Little, Latasha D.
AU - Gumbs, Curtis
AU - Thornton, Rebecca L.
AU - Hudgens, Courtney W.
AU - Chen, Wei Shen
AU - Austin-Breneman, Jacob
AU - Sloane, Robert Szczepaniak
AU - Nezi, Luigi
AU - Cogdill, Alexandria P.
AU - Bernatchez, Chantale
AU - Roszik, Jason
AU - Hwu, Patrick
AU - Woodman, Scott E.
AU - Chin, Lynda
AU - Tawbi, Hussein
AU - Davies, Michael A.
AU - Gershenwald, Jeffrey E.
AU - Amaria, Rodabe N.
AU - Glitza, Isabella C.
AU - Diab, Adi
AU - Patel, Sapna P.
AU - Hu, Jianhua
AU - Lee, Jeffrey E.
AU - Grimm, Elizabeth A.
AU - Tetzlaff, Michael T.
AU - Lazar, Alexander J.
AU - Wistuba, Ignacio I.
AU - Clise-Dwyer, Karen
AU - Carter, Brett W.
AU - Zhang, Jianhua
AU - Futreal, P. Andrew
AU - Sharma, Padmanee
AU - Allison, James P.
AU - Cooper, Zachary A.
AU - Wargo, Jennifer A.
N1 - Publisher Copyright:
© 2017 The Author(s).
PY - 2017/12/1
Y1 - 2017/12/1
N2 - Appreciation for genomic and immune heterogeneity in cancer has grown though the relationship of these factors to treatment response has not been thoroughly elucidated. To better understand this, we studied a large cohort of melanoma patients treated with targeted therapy or immune checkpoint blockade (n = 60). Heterogeneity in therapeutic responses via radiologic assessment was observed in the majority of patients. Synchronous melanoma metastases were analyzed via deep genomic and immune profiling, and revealed substantial genomic and immune heterogeneity in all patients studied, with considerable diversity in T cell frequency, and few shared T cell clones (<8% on average) across the cohort. Variables related to treatment response were identified via these approaches and through novel radiomic assessment. These data yield insight into differential therapeutic responses to targeted therapy and immune checkpoint blockade in melanoma, and have key translational implications in the age of precision medicine.
AB - Appreciation for genomic and immune heterogeneity in cancer has grown though the relationship of these factors to treatment response has not been thoroughly elucidated. To better understand this, we studied a large cohort of melanoma patients treated with targeted therapy or immune checkpoint blockade (n = 60). Heterogeneity in therapeutic responses via radiologic assessment was observed in the majority of patients. Synchronous melanoma metastases were analyzed via deep genomic and immune profiling, and revealed substantial genomic and immune heterogeneity in all patients studied, with considerable diversity in T cell frequency, and few shared T cell clones (<8% on average) across the cohort. Variables related to treatment response were identified via these approaches and through novel radiomic assessment. These data yield insight into differential therapeutic responses to targeted therapy and immune checkpoint blockade in melanoma, and have key translational implications in the age of precision medicine.
UR - http://www.scopus.com/inward/record.url?scp=85028422302&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85028422302&partnerID=8YFLogxK
U2 - 10.1038/s41525-017-0013-8
DO - 10.1038/s41525-017-0013-8
M3 - Article
C2 - 28819565
AN - SCOPUS:85028422302
SN - 2056-7944
VL - 2
JO - npj Genomic Medicine
JF - npj Genomic Medicine
IS - 1
M1 - 10
ER -