Geospatial immune variability illuminates differential evolution of lung adenocarcinoma

AbdulJabbar, K. et al. (2020) Geospatial immune variability illuminates differential evolution of lung adenocarcinoma. Nature Medicine, 26(7), pp. 1054-1062. (doi: 10.1038/s41591-020-0900-x) (PMID:32461698)

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Remarkable progress in molecular analyses has improved our understanding of the evolution of cancer cells toward immune escape1,2,3,4,5. 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 cohort6. 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.

Item Type:Articles
Additional Information:UofG authors Blyth, K.G., Dick, C. and Kidd, A. are members of the TRACERx Consortium.
Glasgow Author(s) Enlighten ID:Dick, Dr Craig and Blyth, Professor Kevin and Le Quesne, Professor John and Kidd, Mr Andrew
Authors: AbdulJabbar, K., Raza, S. E. A., Rosenthal, R., Jamal-Hanjani, M., Veeriah, S., Akarca, A., Lund, T., Moore, D. A., Salgado, R., Al Bakir, M., Zapata, L., Hiley, C. T., Officer, L., Sereno, M., Smith, C. R., Loi, S., Hackshaw, A., Marafioti, T., Quezada, S. A., McGranahan, N., Le Quesne, J., Swanton, C., Yuan, Y., Blyth, K. G., Dick, C., and Kidd, A.
College/School:College of Medical Veterinary and Life Sciences > School of Cancer Sciences
College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
Journal Name:Nature Medicine
Publisher:Nature Research
ISSN (Online):1546-170X
Published Online:27 May 2020
Copyright Holders:Copyright © 2020 The Authors
First Published:First published in Nature Medicine 26(7): 1054-1062
Publisher Policy:Reproduced in accordance with the publisher copyright policy

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