Immunosuppressive niche engineering at the onset of human colorectal cancer

Chandler D. Gatenbee (), Ann-Marie Baker, Ryan O. Schenck, Maximilian Strobl, Jeffrey West, Margarida P. Neves, Sara Yakub Hasan, Eszter Lakatos, Pierre Martinez, William C. H. Cross, Marnix Jansen, Manuel Rodriguez-Justo, Christopher J. Whelan, Andrea Sottoriva, Simon Leedham, Mark Robertson-Tessi, Trevor A. Graham and Alexander R. A. Anderson ()
Additional contact information
Chandler D. Gatenbee: H. Lee Moffitt Cancer Center & Research Institute
Ann-Marie Baker: Barts Cancer Institute, Queen Mary University of London
Ryan O. Schenck: H. Lee Moffitt Cancer Center & Research Institute
Maximilian Strobl: H. Lee Moffitt Cancer Center & Research Institute
Jeffrey West: H. Lee Moffitt Cancer Center & Research Institute
Margarida P. Neves: Barts Cancer Institute, Queen Mary University of London
Sara Yakub Hasan: Barts Cancer Institute, Queen Mary University of London
Eszter Lakatos: Barts Cancer Institute, Queen Mary University of London
Pierre Martinez: Barts Cancer Institute, Queen Mary University of London
William C. H. Cross: Barts Cancer Institute, Queen Mary University of London
Marnix Jansen: University College London Hospital
Manuel Rodriguez-Justo: University College London Hospital
Christopher J. Whelan: H. Lee Moffitt Cancer Center & Research Institute
Andrea Sottoriva: Institute of Cancer Research
Simon Leedham: University of Oxford
Mark Robertson-Tessi: H. Lee Moffitt Cancer Center & Research Institute
Trevor A. Graham: Barts Cancer Institute, Queen Mary University of London
Alexander R. A. Anderson: H. Lee Moffitt Cancer Center & Research Institute

Nature Communications, 2022, vol. 13, issue 1, 1-16

Abstract: Abstract The evolutionary dynamics of tumor initiation remain undetermined, and the interplay between neoplastic cells and the immune system is hypothesized to be critical in transformation. Colorectal cancer (CRC) presents a unique opportunity to study the transition to malignancy as pre-cancers (adenomas) and early-stage cancers are frequently resected. Here, we examine tumor-immune eco-evolutionary dynamics from pre-cancer to carcinoma using a computational model, ecological analysis of digital pathology data, and neoantigen prediction in 62 patient samples. Modeling predicted recruitment of immunosuppressive cells would be the most common driver of transformation. As predicted, ecological analysis reveals that progressed adenomas co-localized with immunosuppressive cells and cytokines, while benign adenomas co-localized with a mixed immune response. Carcinomas converge to a common immune “cold” ecology, relaxing selection against immunogenicity and high neoantigen burdens, with little evidence for PD-L1 overexpression driving tumor initiation. These findings suggest re-engineering the immunosuppressive niche may prove an effective immunotherapy in CRC.

Date: 2022
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-022-29027-8 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-29027-8

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-022-29027-8

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().