Niche engineering drives early passage through an immune bottleneck in progression to colorectal cancer
dc.contributor.author | Gatenbee, C | en_US |
dc.contributor.author | Baker, A-M | en_US |
dc.contributor.author | Schenck, R | en_US |
dc.contributor.author | Neves, M | en_US |
dc.contributor.author | Hasan, SY | en_US |
dc.contributor.author | Martinez, P | en_US |
dc.contributor.author | Cross, WCH | en_US |
dc.contributor.author | Jansen, M | en_US |
dc.contributor.author | Rodriguez-Justo, M | en_US |
dc.contributor.author | Sottoriva, A | en_US |
dc.contributor.author | Leedham, S | en_US |
dc.contributor.author | Robertson-Tessi, M | en_US |
dc.contributor.author | Graham, T | en_US |
dc.contributor.author | Anderson, A | en_US |
dc.date.accessioned | 2019-10-22T09:08:18Z | |
dc.date.issued | 2019-05-03 | en_US |
dc.identifier.uri | https://qmro.qmul.ac.uk/xmlui/handle/123456789/60547 | |
dc.description.abstract | Colorectal cancer develops from its precursor lesion, the adenoma. The immune system is hypothesized to be key in modulating progression, but tumor-immune eco-evolutionary dynamics remain uncharacterized. Here, we demonstrate a key role for immune evasion in the progression of human benign disease to colorectal cancer. We constructed a mathematical model of tumor-immune eco-evolutionary dynamics that predicted ecological succession, from an "immune-hot" adenoma immune ecology rich in T cells to an "immune-cold" carcinoma ecology, deficient in T cells and rich in immunosuppressive cells. Using a cross-sectional cohort of adenomas and carcinomas, we validated this prediction by direct measurement of the tumor-immune ecology using whole-slide 10-marker immunohistochemistry (IHC), and analysis of neoantigen clonal architecture multi-region exome sequencing data. Changes in immune ecology relax selection against antigens with high recognition potentials. This study indicates that immune surveillance represents a key evolutionary bottleneck in the evolution of colon cancer. | en_US |
dc.language.iso | en | en_US |
dc.title | Niche engineering drives early passage through an immune bottleneck in progression to colorectal cancer | en_US |
dc.type | Article | |
dc.rights.holder | (c) the author/funder. 2019. | |
dc.identifier.doi | 10.1101/623959 | en_US |
pubs.notes | Not known | en_US |
pubs.publication-status | Published | en_US |
rioxxterms.funder | Default funder | en_US |
rioxxterms.identifier.project | Default project | en_US |
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