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: | Schools > Medicine Research Institutes & Centres > 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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