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

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 approximately two-fold, compared to those...

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Bibliographic Details
Published in:Cancer letters Vol. 490; pp. 174 - 185
Main Authors: Saleh, Reem, Elkord, Eyad
Format: Journal Article
Language:English
Published: Ireland Elsevier B.V 10.10.2020
Elsevier Limited
Subjects:
Adenosine
Animals
Antigens
biomarker
Biomarkers
Biomarkers, Tumor - immunology
Cancer
Cell cycle
Chemokines
Clinical outcomes
Cytotoxicity
Forkhead protein
Forkhead Transcription Factors - immunology
Foxp3 protein
Homeostasis
Humans
Immune checkpoint inhibitors
Immune response
Immune Tolerance - immunology
Immunoregulation
Immunosuppression
Immunotherapy
Immunotherapy - methods
Lymphocytes
Lymphocytes T
Medical prognosis
Melanoma
Neoplasms - immunology
Ovaries
Peripheral blood
Prognosis
T cell receptors
T-Lymphocyte Subsets - immunology
T-Lymphocytes, Regulatory - immunology
therapeutic target
Thymus gland
Tregs
Tumor Microenvironment - immunology
Tumorigenesis
therapeutic target
biomarker
prognosis
Tregs
Cancer
ISSN:0304-3835, 1872-7980, 1872-7980
Online Access:Get full text
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Summary: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 approximately two-fold, 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 therapy resistance could help in the development of more effective targeted therapeutic strategies to enhance the clinical outcomes in cancer patients. •High FoxP3+ Tregs usually correlate with poor clinical outcomes in cancer patients.•FoxP3+ Treg prognostic effect varies with tumor site and pathological parameters.•Tregs contribute to the development of acquired resistance to immunotherapy.•FoxP3+ Tregs could be prognostic biomarkers and potential therapeutic targets.•Targeting Tregs could improve clinical outcomes and alleviate tumor resistance.
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ISSN:0304-3835
1872-7980
1872-7980
DOI:10.1016/j.canlet.2020.07.022