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

Scurr, Martin John, Ladell, Kristin Ingrid, Besneux, Matthieu, Christian, Adam, Hockey, T., Smart, Kathryn, Bridgeman, Hayley, Hargest, Rachel, Phillips, S., Davies, M., Price, David, Gallimore, Awen Myfanwy and Godkin, Andrew James 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:	13 Feb 2019 21:52
URI:	http://orca.cf.ac.uk/id/eprint/52340

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