Highly prevalent colorectal cancer-infiltrating LAP+ Foxp3- T cells exhibit more potent immunosuppressive activity than Foxp3+ regulatory T cells

Scurr, Martin John ORCID: https://orcid.org/0000-0002-4120-0688, Ladell, Kristin Ingrid ORCID: https://orcid.org/0000-0002-9856-2938, Besneux, Matthieu, Christian, Adam, Hockey, T., Smart, Kathryn, Bridgeman, Hayley, Hargest, Rachel ORCID: https://orcid.org/0000-0001-9830-3832, Phillips, S., Davies, M., Price, David ORCID: https://orcid.org/0000-0001-9416-2737, Gallimore, Awen Myfanwy ORCID: https://orcid.org/0000-0001-6675-7004 and Godkin, Andrew James ORCID: https://orcid.org/0000-0002-1910-7567 2013. Highly prevalent colorectal cancer-infiltrating LAP+ Foxp3- T cells exhibit more potent immunosuppressive activity than Foxp3+ regulatory T cells. Mucosal Immunology n/a 10.1038/mi.2013.62

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Abstract

Although elevated CD4+Foxp3+ regulatory T cell (Treg) frequencies within tumors are well documented, the functional and phenotypic characteristics of CD4+Foxp3+ and CD4+Foxp3− T cell subsets from matched blood, healthy colon, and colorectal cancer require in-depth investigation. Flow cytometry revealed that the majority of intratumoral CD4+Foxp3+ T cells (Tregs) were Helios+ and expressed higher levels of cytotoxic T-lymphocyte antigen 4 (CTLA-4) and CD39 than Tregs from colon and blood. Moreover, ~30% of intratumoral CD4+Foxp3− T cells expressed markers associated with regulatory functions, including latency-associated peptide (LAP), lymphocyte activation gene-3 (LAG-3), and CD25. This unique population of cells produced interleukin-10 (IL-10) and transforming growth factor-β (TGF-β), and was ~50-fold more suppressive than Foxp3+ Tregs. Thus, intratumoral Tregs are diverse, posing multiple obstacles to immunotherapeutic intervention in colorectal malignancies.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine Systems Immunity Research Institute (SIURI)
Subjects:	R Medicine > R Medicine (General) R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Additional Information:	Online publication date: 25 September 2013.
Publisher:	Nature Publishing Group
ISSN:	1933-0219
Funders:	Cancer Research Wales, Wellcome Trust
Date of First Compliant Deposit:	30 March 2016
Last Modified:	11 Oct 2023 19:05
URI:	https://orca.cardiff.ac.uk/id/eprint/52340

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