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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2017-12

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. More... »

PAGES

10

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/s41525-017-0013-8

DOI

http://dx.doi.org/10.1038/s41525-017-0013-8

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1084537792

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/28819565


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594 Department of Stem Cell Transplantation, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, 77030, Houston, TX, USA
595 Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, 77030, Houston, TX, USA
596 Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, 77030, Houston, TX, USA
597 rdf:type schema:Organization
598 https://www.grid.ac/institutes/grid.418152.b schema:alternateName AstraZeneca (United States)
599 schema:name Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, 77030, Houston, TX, USA
600 Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, 77030, Houston, TX, USA
601 MedImmune, 20878, Gaithersburg, MD, USA
602 rdf:type schema:Organization
 




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