Title |
Genomic and immune heterogeneity are associated with differential responses to therapy in melanoma
|
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Published in |
npj Genomic Medicine, April 2017
|
DOI | 10.1038/s41525-017-0013-8 |
Pubmed ID | |
Authors |
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. Little, Curtis 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 |
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. |
X Demographics
Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 4 | 40% |
United Kingdom | 2 | 20% |
Belgium | 1 | 10% |
Unknown | 3 | 30% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 6 | 60% |
Scientists | 2 | 20% |
Practitioners (doctors, other healthcare professionals) | 1 | 10% |
Science communicators (journalists, bloggers, editors) | 1 | 10% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 135 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 30 | 22% |
Researcher | 25 | 19% |
Student > Bachelor | 15 | 11% |
Professor > Associate Professor | 6 | 4% |
Student > Master | 6 | 4% |
Other | 19 | 14% |
Unknown | 34 | 25% |
Readers by discipline | Count | As % |
---|---|---|
Agricultural and Biological Sciences | 25 | 19% |
Biochemistry, Genetics and Molecular Biology | 24 | 18% |
Medicine and Dentistry | 24 | 18% |
Immunology and Microbiology | 11 | 8% |
Engineering | 4 | 3% |
Other | 10 | 7% |
Unknown | 37 | 27% |