期刊
NATURE MEDICINE
卷 26, 期 7, 页码 1054-+出版社
NATURE PORTFOLIO
DOI: 10.1038/s41591-020-0900-x
关键词
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资金
- Cancer Research UK Career Establishment Award [C45982/A21808]
- University College London (UCL) [UCL/12/0279]
- Cancer Research UK [C11496/A17786]
- Breast Cancer Now [2015NovPR638]
- Children's Cancer and Leukaemia Group [CCLGA201906]
- National Institutes of Health (NIH) [U54 CA217376, R01 CA185138]
- CDMRP Breast Cancer Research Program Award [BC132057]
- European Commission ITN (H2020-MSCA-ITN-2019)
- Wellcome Trust [105104/Z/14/Z, FC001169, FC001202]
- Royal Marsden/ICR National Institute of Health Research Biomedical Research Centre
- Francis Crick Institute from Cancer Research UK [FC001169, FC001202]
- UK Medical Research Council [FC001169, FC001202]
- Cancer Research UK (TRACERx)
- Cancer Research UK (PEACE)
- Cancer Research UK (Cancer Research UK Cancer Immunotherapy Catalyst Network)
- Cancer Research UK Lung Cancer Centre of Excellence
- Rosetrees Trust
- NovoNordisk Foundation [ID16584]
- Breast Cancer Research Foundation
- Stand Up To Cancer-LUNGevity-American Lung Association Lung Cancer Interception Dream Team Translational Research Grant [SU2C-AACR-DT23-17]
- American Association for Cancer Research
- Scientific Partner of SU2C
- European Research Council (ERC) under the European Union [617844]
- European Commission ITN [FP7-PloidyNet 607722]
- ERC Advanced Grant (PROTEUS) from the European Research Council under the European Union's Horizon 2020 Research and Innovation Programme [835297]
- European Union [665233]
- Cancer Research UK Senior Cancer Research Fellowship [C36463/A22246]
- Cancer Research UK Biotherapeutic Program Grant [C36463/A20764]
- National Breast Cancer Foundation of Australia Endowed Chair
- Breast Cancer Research Foundation, New York
- European Union's Horizon 2020 Research and Innovation Programme under the Marie Sklodowska-Curie grant [846614]
- UCL Biomedical Research Council
- Cancer Research UK
- NIH Research
- UKI NETs
- MRC [MR/P014712/1] Funding Source: UKRI
- The Francis Crick Institute [10233] Funding Source: researchfish
- Wellcome Trust [105104/Z/14/Z] Funding Source: researchfish
- European Research Council (ERC) [617844] Funding Source: European Research Council (ERC)
- Marie Curie Actions (MSCA) [846614] Funding Source: Marie Curie Actions (MSCA)
Remarkable progress in molecular analyses has improved our understanding of the evolution of cancer cells toward immune escape(1-5). However, the spatial configurations of immune and stromal cells, which may shed light on the evolution of immune escape across tumor geographical locations, remain unaddressed. We integrated multiregion exome and RNA-sequencing (RNA-seq) data with spatial histology mapped by deep learning in 100 patients with non-small cell lung cancer from the TRACERx cohort(6). Cancer subclones derived from immune cold regions were more closely related in mutation space, diversifying more recently than subclones from immune hot regions. In TRACERx and in an independent multisample cohort of 970 patients with lung adenocarcinoma, tumors with more than one immune cold region had a higher risk of relapse, independently of tumor size, stage and number of samples per patient. In lung adenocarcinoma, but not lung squamous cell carcinoma, geometrical irregularity and complexity of the cancer-stromal cell interface significantly increased in tumor regions without disruption of antigen presentation. Decreased lymphocyte accumulation in adjacent stroma was observed in tumors with low clonal neoantigen burden. Collectively, immune geospatial variability elucidates tumor ecological constraints that may shape the emergence of immune-evading subclones and aggressive clinical phenotypes. Multiregion spatial histology, exome and transcriptome data from patients with non-small cell lung cancer suggest that cancer subclones from immune cold regions diversify later than subclones from immune hot regions
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