Immune checkpoint inhibitor-induced colitis is mediated by polyfunctional lymphocytes and is dependent on an IL23/IFNγ axis

Jonathan W. Lo, Domenico Cozzetto, James L. Alexander, Nathan P. Danckert, Matthew Madgwick, Naomi Knox, Jillian Yong Xin Sieh, Marton Olbei, Zhigang Liu, Hajir Ibraheim, Jesus Miguens Blanco, Hiromi Kudo, Rocio Castro Seoane, Lucia A. Possamai, Robert Goldin, Julian Marchesi, Tamas Korcsmaros, Graham M. Lord and Nick Powell ()
Additional contact information
Jonathan W. Lo: Imperial College London
Domenico Cozzetto: Imperial College London
James L. Alexander: Imperial College London
Nathan P. Danckert: Imperial College London
Matthew Madgwick: Organisms and Ecosystems, Earlham Institute
Naomi Knox: Imperial College London
Jillian Yong Xin Sieh: King’s College London
Marton Olbei: Imperial College London
Zhigang Liu: Imperial College London
Hajir Ibraheim: Imperial College London
Jesus Miguens Blanco: Imperial College London
Hiromi Kudo: Imperial College London
Rocio Castro Seoane: Imperial College London
Lucia A. Possamai: Imperial College London
Robert Goldin: Imperial College London
Julian Marchesi: Imperial College London
Tamas Korcsmaros: Imperial College London
Graham M. Lord: King’s College London
Nick Powell: Imperial College London

Nature Communications, 2023, vol. 14, issue 1, 1-20

Abstract: Abstract Immune checkpoint inhibitors (CPIs) are a relatively newly licenced cancer treatment, which make a once previously untreatable disease now amenable to a potential cure. Combination regimens of anti-CTLA4 and anti-PD-1 show enhanced efficacy but are prone to off-target immune-mediated tissue injury, particularly at the barrier surfaces. To probe the impact of immune checkpoints on intestinal homoeostasis, mice are challenged with anti-CTLA4 and anti-PD-1 immunotherapy and manipulation of the intestinal microbiota. The immune profile of the colon of these mice with CPI-colitis is analysed using bulk RNA sequencing, single-cell RNA sequencing and flow cytometry. CPI-colitis in mice is dependent on the composition of the intestinal microbiota and by the induction of lymphocytes expressing interferon-γ (IFNγ), cytotoxicity molecules and other pro-inflammatory cytokines/chemokines. This pre-clinical model of CPI-colitis could be attenuated following blockade of the IL23/IFNγ axis. Therapeutic targeting of IFNγ-producing lymphocytes or regulatory networks, may hold the key to reversing CPI-colitis.

Date: 2023
References: View references in EconPapers View complete reference list from CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/s41467-023-41798-2 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:14:y:2023:i:1:d:10.1038_s41467-023-41798-2

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

DOI: 10.1038/s41467-023-41798-2

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 ().