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Cited by 286

The DOI matches its Crossref record; 10 of the 10 references it cites were found in a registry or an index.

Geospatial immune variability illuminates differential evolution of lung adenocarcinoma

Open access
TRACERx Consortium, AbdulJabbar, Khalid, Raza, Shan E. Ahmed, Rosenthal, Rachel, Jamal-Hanjani, Mariam, Veeriah, Selvaraju, Akarca, Ayse, Lund, Tom, Moore, David A., Salgado, Roberto, Al Bakir, Maise, Zapata, Luis, Hiley, Crispin T., Officer, Leah, Sereno, Marco, Smith, Claire Rachel, Loi, Sherene, Hackshaw, Allan, Marafioti, Teresa, Quezada, Sergio A., McGranahan, Nicholas, Le Quesne, John, Swanton, Charles, Yuan, Yinyin·2020·Nature Medicine
DOI 10.1038/s41591-020-0900-x
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Abstract

Remarkable progress in molecular analyses has improved our understanding of the evolution of cancer cells toward immune escape1–5. 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. 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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Citations

Cites

Research works printed but not linked: 29

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Metadata

Authors
TRACERx Consortium, 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.
Venue
Nature Medicine
Publisher
Springer Science and Business Media LLC
Published
2020-05-27
Volume
26
Issue
7
Pages
1054-1062
ISSN
  • 1078-8956 (ISSN-L)
  • 1546-170X
DOI
10.1038/s41591-020-0900-x
OpenAlex
W3031256816
Cited by
286
References
10
FWCI
13.09
Type
journal article
Language
en
Open access
green
Licence

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