The Role of Tregs in Cancer: Foxp3 as a Putative Target for Therapy

Brendan      Meyer; Wai   M.   Liu; Angus   G.   Dalgleish; Christine      Galustian

doi:10.2174/157436209788167475

Abstract

There is increasing evidence to support the idea that immune modulation is involved in cancer progression. Indeed, the growth in the number of publications describing cancer immunotherapy and how it impacts on cell signaling pathways reinforces this idea. In particular, the forkhead box P3 (Foxp3) transcription factor is an important protagonist in regulatory T cell (Treg) suppression, which has recently been reported to be mediated by the PI3-kinase/AKT/mTOR and TGF-β signaling cascades. This could provide an exciting facet of carcinogenesis, by linking modulation of immuneeffector cells and tumourogenesis of cancer cells. Furthermore, recent findings have indicated a direct role for Foxp3 within tumour cells, and its expression in Tregs has been used as an indicator of poor prognosis in cancer patients. Therapeutic modulation of these systems thus provides an attractive approach to cancer treatment. Additionally, drugcombination strategies utilising agents that target signaling pathways may prove beneficial by simultaneously targeting tumour and immune cells, thereby enhancing native immune response to growing tumours. This article will review the factors involved in Foxp3 expression and highlight the means by which Foxp3-expressing cells could be targeted as a part of cancer immunotherapy.

Keywords: Foxp3, regulatory T cell, cancer, signaling, target, therapy