Epigenetically driven and early immune evasion in colorectal cancer evolution
Artikel i vetenskaplig tidskrift, 2025
Immune system control is a principal hurdle in cancer evolution. The temporal dynamics of immune evasion remain incompletely characterized, and how immune-mediated selection interrelates with epigenome alteration is unclear. Here we infer the genome- and epigenome-driven evolutionary dynamics of tumor-immune coevolution within primary colorectal cancers (CRCs). We utilize a multiregion multiomic dataset of matched genome, transcriptome and chromatin accessibility profiling from 495 single glands (from 29 CRCs) supplemented with high-resolution spatially resolved neoantigen sequencing data and multiplexed imaging of the tumor microenvironment from 82 microbiopsies within 11 CRCs. Somatic chromatin accessibility alterations contribute to accessibility loss of antigen-presenting genes and silencing of neoantigens. Immune escape and exclusion occur at the outset of CRC formation, and later intratumoral differences in immuno-editing are negligible or exclusive to sites of invasion. Collectively, immune evasion in CRC follows a 'Big Bang' evolutionary pattern, whereby it is acquired close to transformation and defines subsequent cancer-immune evolution.
Författare
[Person d263dd31-b229-4b32-98a5-ecf111f0463c not found]
Göteborgs universitet
Chalmers, Matematiska vetenskaper, Tillämpad matematik och statistik
[Person 69e2502d-4cbc-4e69-a5d8-2682ddf9bf06 not found]
Queen Mary University of London
University College London (UCL)
[Person fab2f490-3ec0-4dba-85a8-8fb37b7993bc not found]
Institute of Cancer Research
Arizona State University
[Person ddbf6cfc-658d-43d5-a71d-9477b52a21d8 not found]
Institute of Cancer Research
[Person d8151c7a-4428-48ac-87f5-1e1aadf45fce not found]
Human Technopole
Institute of Cancer Research
[Person 5628fadb-4505-4bf0-9333-98d01d4f61b3 not found]
University College London (UCL)
Institute of Cancer Research
[Person 6576cecb-3b27-4187-adc0-d9ba01ab1ce6 not found]
Queen Mary University of London
[Person 4a4b5917-2e13-4ce4-88c9-67815cbd909e not found]
Arizona State University
[Person 20554f1e-c707-4802-a79f-9576cffa97ca not found]
Institute of Cancer Research
[Person e1f09a38-d6d8-48d6-a4c0-98db4bfa04e7 not found]
Queen Mary University of London
Institute of Cancer Research
[Person 3e232074-ad78-452b-af40-c09247dfb68f not found]
Queen Mary University of London
[Person 857405c8-cf53-4d59-aac6-e97ca25b9623 not found]
Institute of Cancer Research
[Person 1134dce1-68ee-41f7-bd23-e818679c684b not found]
Institute of Cancer Research
St. Anna Children's Cancer Research Institute (CCRI)
[Person 5b095c0d-4f83-4b78-bec8-ea54ed502f52 not found]
Queen Mary University of London
[Person 88a31115-2cfb-4a31-b17e-92482a5e4932 not found]
University College London (UCL)
[Person 84997567-46d0-45b8-865c-bce175665650 not found]
Arizona State University
[Person da54447e-820e-4cef-af4e-7bdc9dcbee13 not found]
University College London (UCL)
[Person ccb3aa0f-b387-482c-a667-df874eb1abeb not found]
University College London (UCL)
[Person 21ff73ec-af48-46a0-b707-110275156cb2 not found]
University College London (UCL)
[Person 715816bf-1dbb-4d34-a29b-eb98b68fc72d not found]
Institute of Cancer Research
Queen Mary University of London
[Person ec38c0e9-7dc0-4706-99be-9a55cb7326c2 not found]
Institute of Cancer Research
Human Technopole
[Person b6e63241-e4c4-4634-8838-a7efb991ee84 not found]
Queen Mary University of London
Institute of Cancer Research
Nature Genetics
1061-4036 (ISSN) 15461718 (eISSN)
Vol. 57 12 3039-3049Studera resistensutveckling genom att utnyttja vätskebiopsier
Vetenskapsrådet (VR) (2024-04145), 2025-01-01 -- 2028-12-31.
Styrkeområden
Hälsa och teknik
Ämneskategorier (SSIF 2025)
Cancer och onkologi
DOI
10.1038/s41588-025-02349-1
PubMed
41193656