The Regulation of FOXP3 Expression and Its Therapeutic Potential in Non-Small Lung Cancer

Abstract

Non-small cell cancer (NSCLC) is today one of the most threatening malignant tumors, and it is still rarely cured by current standard therapies with a high mortality rate. The transcription factor Forkhead box p3 (FOXP3) is a potential molecular target for NSCLC since it has been identified with an oncogenic effect in the tumor microenvironment (TME). It is well known that FOXP3 expression could characterize the regulatory T cells (Treg), which plays a critical role in regulating anti-tumor immune responses in TME. Through analyzing the basic mechanisms of FOXP3 and Treg in distinct tumor tissues, they have been found with contradictory expression and the frequency in different TME. In NSCLC, the suppressive function of Treg to immune systems and frequency of FOXP3 is accumulated to promote the development of tumors. Most recently, accumulating evidence reveals the therapeutic potential of targeting FOXP3 and the related signaling pathways in the treatment of NSCLC patients. Although unsolved side effects and limitations that still must be considered when targeting FOXP3 and FOXP3-related proteins, there is no doubt that they are potential therapeutic applications for NSCLC treatment. The main objective of this review is to mention the structure, function and recent progress in treatment targeting FOXP3 and FOXP3-related signaling pathways, especially to therapies with immune checkpoint inhibitors.