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

Alexandre Reuben, Christine N. Spencer, Peter A. Prieto, Vancheswaran Gopalakrishnan, Sangeetha M. Reddy, John P. Miller, Xizeng Mao, Mariana Petaccia De Macedo, Jiong Chen, Xingzhi Song, Hong Jiang, Pei Ling Chen, Hannah C. Beird, Haven R. Garber, Whijae Roh, Khalida Wani, Eveline Chen, Cara Haymaker, Marie Andrée Forget, Latasha D. LittleCurtis Gumbs, Rebecca L. Thornton, Courtney W. Hudgens, Wei Shen Chen, Jacob Austin-Breneman, Robert Szczepaniak Sloane, Luigi Nezi, Alexandria P. Cogdill, Chantale Bernatchez, Jason Roszik, Patrick Hwu, Scott E. Woodman, Lynda Chin, Hussein Tawbi, Michael A. Davies, Jeffrey E. Gershenwald, Rodabe N. Amaria, Isabella C. Glitza, Adi Diab, Sapna P. Patel, Jianhua Hu, Jeffrey E. Lee, Elizabeth A. Grimm, Michael T. Tetzlaff, Alexander J. Lazar, Ignacio I. Wistuba, Karen Clise-Dwyer, Brett W. Carter, Jianhua Zhang, P. Andrew Futreal, Padmanee Sharma, James P. Allison, Zachary A. Cooper, Jennifer A. Wargo

Research output: Contribution to journalArticle

38 Scopus citations

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.

Original languageEnglish (US)
Article number10
Journalnpj Genomic Medicine
Volume2
Issue number1
DOIs
StatePublished - Dec 1 2017
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

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    Reuben, A., Spencer, C. N., Prieto, P. A., Gopalakrishnan, V., Reddy, S. M., Miller, J. P., Mao, X., De Macedo, M. P., Chen, J., Song, X., Jiang, H., Chen, P. L., Beird, H. C., Garber, H. R., Roh, W., Wani, K., Chen, E., Haymaker, C., Forget, M. A., ... Wargo, J. A. (2017). Genomic and immune heterogeneity are associated with differential responses to therapy in melanoma. npj Genomic Medicine, 2(1), [10]. https://doi.org/10.1038/s41525-017-0013-8