FOXP3 and Its Cofactors as Targets of Immunotherapies

Yasuhiro Nagai, Lian Lam, Mark I. Greene, Hongtao Zhang

Engineering ›› 2019, Vol. 5 ›› Issue (1) : 115-121.

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Engineering ›› 2019, Vol. 5 ›› Issue (1) : 115-121. DOI: 10.1016/j.eng.2019.01.001
Research
Review Immunology—Review

FOXP3 and Its Cofactors as Targets of Immunotherapies

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Abstract

Forkhead box P3 (FOXP3) is a “master regulator” of regulatory T cells (Tregs), which are a subset of T cells that can suppress the antigen-specific immune reaction and that play important roles in host tolerance and immune homeostasis. It is well known that FOXP3 forms complexes with several proteins and can be regulated by various post-translational modifications (PTMs) such as acetylation, phosphorylation, ubiquitination, and methylation. As a consequence, the PTMs change the stability of FOXP3 and its capability to regulate gene expression, and eventually affect Treg activity. Although FOXP3 per se is not an ideal drug target, deacetylases, acetyltransferases, kinases, and other enzymes that regulate the PTMs of FOXP3 are potential targets to modulate FOXP3 and Treg activity. However, FOXP3 is not the only substrate for most of these enzymes; thus, unwanted “on target/off FOXP3” side effects must be considered when inhibitors to these enzymes are used. In this review, we summarize recent progress in the study of FOXP3 cofactors and PTM proteins, and potential clinical applications in autoimmunity and cancer immunity.

Keywords

Treg / Forkhead box P3 (FOXP3) / Post-translational modification / Autoimmune / Cancer

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Yasuhiro Nagai, Lian Lam, Mark I. Greene, Hongtao Zhang. FOXP3 and Its Cofactors as Targets of Immunotherapies. Engineering, 2019, 5(1): 115‒121 https://doi.org/10.1016/j.eng.2019.01.001

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Acknowledgement

We acknowledge grant supports from the Breast Cancer Research Foundation and the National Institutes of Health to M.I. Greene (RO1CA219034).

Compliance with ethics guidelines

Yasuhiro Nagai, Lian Lam, Mark I. Greene, and Hongtao Zhang declare that they have no conflict of interest or financial conflicts to disclose.

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