Niche engineering drives early passage through an immune bottleneck in progression to colorectal cancer

Gatenbee, C. D.; Baker, A.-M.; Schenck, R. O.; Neves, M.; Hasan, S. Y.; Martinez, P.; Cross, W. C. H.; Jansen, M.; Rodriguez-Justo, M.; Sottoriva, A.; Leedham, S.; Robertson-Tessi, M.; Graham, T. A.; Anderson, A.

doi:10.1101/623959

bioRxiv · 10.1101/623959

Niche engineering drives early passage through an immune bottleneck in progression to colorectal cancer

Gatenbee, C. D.·Baker, A.-M.·Schenck, R. O.·Neves, M.·Hasan, S. Y.·Martinez, P.·Cross, W. C. H.·Jansen, M.·Rodriguez-Justo, M.·Sottoriva, A.·Leedham, S.·Robertson-Tessi, M.·Graham, T. A.·Anderson, A.

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Abstract

O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=200 SRC=\"FIGDIR/small/623959v2_ufig1.gif\" ALT=\"Figure 1\">\nView larger version (55K):\norg.highwire.dtl.DTLVardef@1c48cf5org.highwire.dtl.DTLVardef@1026747org.highwire.dtl.DTLVardef@ca92f1org.highwire.dtl.DTLVardef@1753cd5_HPS_FORMAT_FIGEXP M_FIG C_FIG 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.

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Gatenbee, C. D., Baker, A.-M., Schenck, R. O., Neves, M., Hasan, S. Y., Martinez, P., Cross, W. C. H., Jansen, M., Rodriguez-Justo, M., Sottoriva, A., Leedham, S., Robertson-Tessi, M., Graham, T. A., Anderson, A.. 2019-05-03. Niche engineering drives early passage through an immune bottleneck in progression to colorectal cancer. https://doi.org/10.1101/623959

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