期刊
CELL REPORTS MEDICINE
卷 1, 期 8, 页码 -出版社
CELL PRESS
DOI: 10.1016/j.xcrm.2020.100139
关键词
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资金
- Bristol-Myers Squibb
- US National Institutes of Health [CA121113, CA233259, CA006973, CA142779]
- Commonwealth Foundation
- Bloomberg-Kimmel Institute for Cancer Immunotherapy
- Dr. Miriam and Sheldon G. Adelson Medical Research Foundation
- V Foundation
- Swim Across America
- Allegheny Health Network -Johns Hopkins Research Fund
- LUNGevity Foundation
- Mark Foundation For Cancer Research
- Barney Foundation
- Moving for Melanoma of Delaware
- Laverna Hahn Charitable Trust
- Melanoma Research Alliance
- Cancer Immunology Translational Cancer Research Grant from Cancer Research Institute-Stand Up 2 Cancer [SU2C-AACR-DT1012]
In this study, we incorporate analyses of genome-wide sequence and structural alterations with pre- and ontherapy transcriptomic and T cell repertoire features in immunotherapy-naive melanoma patients treated with immune checkpoint blockade. Although tumor mutation burden is associated with improved treatment response, the mutation frequency in expressed genes is superior in predicting outcome. Increased T cell density in baseline tumors and dynamic changes in regression or expansion of the T cell repertoire during therapy distinguish responders from non-responders. Transcriptome analyses reveal an increased abundance of B cell subsets in tumors from responders and patterns of molecular response related to expressed mutation elimination or retention that reflect clinical outcome. High-dimensional genomic, transcriptomic, and immune repertoire data were integrated into a multi-modal predictor of response. These findings identify genomic and transcriptomic characteristics of tumors and immune cells that predict response to immune checkpoint blockade and highlight the importance of pre-existing T and B cell immunity in therapeutic outcomes.
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