期刊
NATURE MEDICINE
卷 25, 期 10, 页码 1549-+出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/s41591-019-0592-2
关键词
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资金
- Cancer Immunotherapy Accelerator Award [C33499/A20265]
- CRUK's Lung Cancer Centre of Excellence [C5759/A20465]
- National Institute for Health Research UCL Hospitals Biomedical Research Centre
- Cancer Research UK (CRUK)
- CRUK Senior Cancer Research Fellowship [C36463/A22246]
- Sam Keen Foundation
- Institute of Cancer Research Biomedical Research Centre
- Royal Marsden Cancer Charity
- UCL Biomedical Research Centre
- Cancer Research UK studentship
- MRC Clinical Infrastructure award [MR/M009033/1]
- Rosetrees and Stoneygate Trust [A1388]
- CRUK Biotherapeutics Programme grant [C36463/A20764]
- Khoo Teck Puat UK Foundation via the UCL Cancer Institute Research Trust [539288]
- ERC [StG 677268 NextDART]
- Royal Society Napier Research Professor
- Francis Crick Institute
- Cancer Research UK
- UK Medical Research Council [FC001169]
- Wellcome Trust [FC001169]
- CRUK Cancer Immunotherapy Catalyst Network
- CRUK Lung Cancer Centre of Excellence, Stand Up 2 Cancer (SU2C)
- Rosetrees Trust
- Stoneygate Trusts
- NovoNordisk Foundation [ID16584]
- Prostate Cancer Foundation
- Breast Cancer Research Foundation (BCRF)
- European Research Council (ERC) [FP7-THESEUS-617844]
- European Commission ITN [607722]
- ERC Advanced Grant (PROTEUS) from the European Research Council under the European Union [835297]
- National Institute for Health Research
- University College London Hospitals Biomedical Research Centre
- Cancer Research UK University College London Experimental Cancer Medicine Centre
- MRC [MR/N000838/1, MR/M009033/1] Funding Source: UKRI
- The Francis Crick Institute [10233] Funding Source: researchfish
Somatic mutations together with immunoediting drive extensive heterogeneity within non-small-cell lung cancer (NSCLC). Herein we examine heterogeneity of the T cell antigen receptor (TCR) repertoire. The number of TCR sequences selectively expanded in tumors varies within and between tumors and correlates with the number of nonsynonymous mutations. Expanded TCRs can be subdivided into TCRs found in all tumor regions (ubiquitous) and those present in a subset of regions (regional). The number of ubiquitous and regional TCRs correlates with the number of ubiquitous and regional nonsynonymous mutations, respectively. Expanded TCRs form part of clusters of TCRs of similar sequence, suggestive of a spatially constrained antigen-driven process. CD8(+) tumor-infiltrating lymphocytes harboring ubiquitous TCRs display a dysfunctional tissue-resident phenotype. Ubiquitous TCRs are preferentially detected in the blood at the time of tumor resection as compared to routine follow-up. These findings highlight a noninvasive method to identify and track relevant tumor-reactive TCRs for use in adoptive T cell immunotherapy.
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