Turning the Tide Against Regulatory T Cells

In this study, T cells deficient in TRAF6 display enhanced T cell activation, CD28-indpendent stimulation and resistance to Treg cell-mediated suppression (176). Although TLR signaling can promote T cell resistance to Treg cells, the precise molecular mechanism remains yet to be elucidated. It is worth noting that TLR stimulation of T cells increases cytokine production (173, 177), thus future studies should delineate the effect of TLR-MyD88 signaling vs. subsequently induced cytokines in generating resistance to Treg cells. Lastly, it is also crucial to evaluate the effect of TLR signaling on regulatory T cells which also express TLRs (170). The role of TLR signaling on Treg cell function requires further investigation and clarification since it can both abrogate and enhance Treg cell functions (170, 177–179). A recent study suggested that TLR signaling on regulatory T cells induces PI3K/Akt/mTORC1 signaling which subsequently increases glycolysis and GLUT1 expression, which in turn interferes with FoxP3 expression and the suppressive ability of Treg cells (180). However, increased Treg cell function observed in several studies could also occur indirectly as a result of enhanced T cell stimulation and IL-2 secretion, which can subsequently promote Treg cell function. Although TLR agonists can improve anti-tumor immune responses by enhancing T cell function and/or stimulating APC maturation, they may also act on other immune cells and cancer cells to impact anti-tumo...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research