Genomic and immune heterogeneity are associated with differential responses to therapy in melanoma

Alexandre Reuben(The University of Texas MD Anderson Cancer Center), Christine N. Spencer(The University of Texas MD Anderson Cancer Center), Peter A. Prieto(The University of Texas MD Anderson Cancer Center), Vancheswaran Gopalakrishnan(The University of Texas MD Anderson Cancer Center), Sangeetha M. Reddy(The University of Texas MD Anderson Cancer Center), John P. Miller(The University of Texas MD Anderson Cancer Center), Xizeng Mao(The University of Texas MD Anderson Cancer Center), Mariana Petaccia de Macêdo(The University of Texas MD Anderson Cancer Center), Jiong Chen(The University of Texas MD Anderson Cancer Center), Xingzhi Song(The University of Texas MD Anderson Cancer Center), Hong Jiang(The University of Texas MD Anderson Cancer Center), Pei-Ling Chen(The University of Texas MD Anderson Cancer Center), Hannah C. Beird(The University of Texas MD Anderson Cancer Center), Haven R. Garber(The University of Texas MD Anderson Cancer Center), Whijae Roh(The University of Texas MD Anderson Cancer Center), Khalida Wani(The University of Texas MD Anderson Cancer Center), Eveline Chen(The University of Texas MD Anderson Cancer Center), Cara Haymaker(The University of Texas MD Anderson Cancer Center), Marie‐Andrée Forget(The University of Texas MD Anderson Cancer Center), Latasha Little(The University of Texas MD Anderson Cancer Center), Curtis Gumbs(The University of Texas MD Anderson Cancer Center), Rebecca Thornton(The University of Texas MD Anderson Cancer Center), Courtney W. Hudgens(The University of Texas MD Anderson Cancer Center), Wei‐Shen Chen(The University of Texas MD Anderson Cancer Center), Jacob L. Austin-Breneman(The University of Texas MD Anderson Cancer Center), Robert Szczepaniak‐Sloane(The University of Texas MD Anderson Cancer Center), Luigi Nezi(The University of Texas MD Anderson Cancer Center), Alexandria P. Cogdill(The University of Texas MD Anderson Cancer Center), Chantale Bernatchez(The University of Texas MD Anderson Cancer Center), Jason Roszik(The University of Texas MD Anderson Cancer Center), Patrick Hwu(The University of Texas MD Anderson Cancer Center), Scott E. Woodman(The University of Texas MD Anderson Cancer Center), Lynda Chin(The University of Texas MD Anderson Cancer Center), Hussein A. Tawbi(The University of Texas MD Anderson Cancer Center), Michael A. Davies(The University of Texas MD Anderson Cancer Center), Jeffrey E. Gershenwald(The University of Texas MD Anderson Cancer Center), Rodabe N. Amaria(The University of Texas MD Anderson Cancer Center), Isabella C. Glitza(The University of Texas MD Anderson Cancer Center), Adi Diab(The University of Texas MD Anderson Cancer Center), Sapna P. Patel(The University of Texas MD Anderson Cancer Center), Jianhua Hu(The University of Texas MD Anderson Cancer Center), Jeffrey E. Lee(The University of Texas MD Anderson Cancer Center), Elizabeth A. Grimm(The University of Texas MD Anderson Cancer Center), Michael T. Tetzlaff(The University of Texas MD Anderson Cancer Center), Alexander J. Lazar(The University of Texas MD Anderson Cancer Center), Ignacio I. Wistuba(The University of Texas MD Anderson Cancer Center), Karen Clise-Dwyer(The University of Texas MD Anderson Cancer Center), Brett W. Carter(The University of Texas MD Anderson Cancer Center), Jianhua Zhang(The University of Texas MD Anderson Cancer Center), P. Andrew Futreal(The University of Texas MD Anderson Cancer Center), Padmanee Sharma(The University of Texas MD Anderson Cancer Center), James P. Allison(The University of Texas MD Anderson Cancer Center), Zachary A. Cooper(The University of Texas MD Anderson Cancer Center), Jennifer A. Wargo(The University of Texas MD Anderson Cancer Center)
npj Genomic Medicine
April 3, 2017
10.1038/s41525-017-0013-8
Cited by 188Open Access
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Abstract

Abstract 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.

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