FoxP3+ T regulatory cells in cancer : prognostic biomarkers and therapeutic targets

Saleh, R; Elkord, E

Abstract

T Regulatory cells (Tregs) can have both protective and pathological roles. They maintain immune homeostasis and inhibit immune responses in various diseases, including cancer. Proportions of Tregs in the peripheral blood of some cancer patients increase by five-to ten-folds, compared to those in healthy individuals. Tregs contribute to cancer development and progression by suppressing T effector cell functions, thereby compromising tumor killing and promoting tumor growth. Highly immunosuppressive Tregs express upregulated levels of the transcription factor, Forkhead box protein P3 (FoxP3). Elevated levels of FoxP3+ Tregs within the tumor microenvironment (TME) showed a positive correlation with poor prognosis in various cancer patients. Despite the success of immunotherapy, including the use of immune checkpoint inhibitors, a significant proportion of patients show low response rates as a result of primary or acquired resistance against therapy. Some of the mechanisms which underlie the development of therapy resistance are associated with Treg suppressive function. In this review, we describe Treg contribution to cancer development/progression, and the mechanisms of Treg-mediated immunosuppression. We discuss the prognostic significance of FoxP3+ Tregs in different cancers and their potential use as prognostic biomarkers. We also describe potential therapeutic strategies to target Tregs in combination with other types of immunotherapies aiming to overcome tumor resistance and improve clinical outcomes in cancer patients. Overall, understanding the prognostic significance of FoxP3+ Tregs in various cancers and their contribution to therapeutic resistance could help in the development of more effective targeted therapeutic strategies to enhance the clinical outcomes in cancer patients.

Citation

Saleh, R., & Elkord, E. (2020). FoxP3+ T regulatory cells in cancer : prognostic biomarkers and therapeutic targets. Cancer Letters, 490, 174-185. https://doi.org/10.1016/j.canlet.2020.07.022

• Journal Article Type: Article
• Acceptance Date: Jul 16, 2020
• Online Publication Date: Jul 25, 2020
• Publication Date: Oct 10, 2020
• Deposit Date: Aug 4, 2020
• Publicly Available Date: Aug 4, 2020
• Journal: Cancer Letters
• Print ISSN: 0304-3835
• Publisher: Elsevier
• Volume: 490
• Pages: 174-185
• DOI: https://doi.org/10.1016/j.canlet.2020.07.022
• Publisher URL: https://doi.org/10.1016/j.canlet.2020.07.022
• Related Public URLs: http://www.journals.elsevier.com/cancer-letters/
• Additional Information: Additional Information : ** Article version: AM ** From Elsevier via Jisc Publications Router ** Licence for AM version of this article starting on 25-07-2020: http://creativecommons.org/licenses/by/4.0/ **Journal IDs: issn 03043835 **History: issue date 25-07-2020; accepted 16-07-2020; Funders : Qatar Biomedical research Institute, Qatar Foundation;Qatar National Library