Geospatial immune variability illuminates differential evolution of lung adenocarcinoma

Autor: Tom Lund, Roberto Salgado, Rachel Rosenthal, Shan E Ahmed Raza, Marco Sereno, Sergio A. Quezada, Claire Rachel Smith, Selvaraju Veeriah, Leah Officer, Mariam Jamal-Hanjani, Nicholas McGranahan, David Moore, Yinyin Yuan, Maise Al Bakir, Allan Hackshaw, Crispin T. Hiley, Sherene Loi, Luis Zapata, John Le Quesne, Charles Swanton, Teresa Marafioti, Ayse Akarca, Khalid AbdulJabbar
Rok vydání: 2020
Předmět:
0301 basic medicine
Exome/genetics
Male
Tumour heterogeneity
Mutation/genetics
Tumor Microenvironment/genetics
Lymphocyte
Antigen presentation
Adenocarcinoma of Lung
Biology
Article
General Biochemistry
Genetics and Molecular Biology
Adenocarcinoma of Lung/genetics
Whole Exome Sequencing
03 medical and health sciences
0302 clinical medicine
Immune system
Deep Learning
Antigen
Antigens
Neoplasm
Recurrence
Carcinoma
Non-Small-Cell Lung
Carcinoma
Non-Small-Cell Lung/genetics
Exome Sequencing
Biomarkers
Tumor
Tumor Microenvironment
medicine
Humans
Exome
RNA-Seq
Neoplasm Staging
Tumor microenvironment
Cancer
General Medicine
Middle Aged
medicine.disease
Antigens
Neoplasm/genetics
030104 developmental biology
medicine.anatomical_structure
030220 oncology & carcinogenesis
Mutation
Cancer research
Adenocarcinoma
Female
Neoplasm Recurrence
Local
Biomarkers
Tumor/genetics
Neoplasm Recurrence
Local/genetics
RC
Zdroj: Nature Medicine
TRACERx Consortium & Blackhall, F 2020, ' Geospatial immune variability illuminates differential evolution of lung adenocarcinoma ', Nature Medicine, vol. 26, no. 7, pp. 1054-1062 . https://doi.org/10.1038/s41591-020-0900-x
Nat Med
ISSN: 1078-8956
DOI: 10.1038/s41591-020-0900-x
Popis: Remarkable progress in molecular analyses has improved our understanding of the evolution of cancer cells towards 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 multi-region exome and RNA-seq data with spatial histology mapped by deep learning in 100 non-small cell lung cancer (NSCLC) patients from the TRAcking Cancer Evolution through Therapy (Rx) (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 multi-sample cohort of 970 lung adenocarcinoma (LUAD) patients, the number of immune cold regions significantly correlated with risk of relapse, independently of tumor size, stage and number of samples per patient. In LUAD, but not lung squamous cell carcinoma (LUSC), 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.
Databáze: OpenAIRE
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