New research from the Varelas laboratory describes novel roles for the Hippo pathway effector YAP in T cells has been published in PLOS Biology: Yap suppresses T-cell function and infiltration in the tumor microenvironment
This study describes previously unappreciated functions for the signaling effector YAP in T cells. Stampouloglou et al., describe immunoinhibitory functions for YAP in CD4+ and CD8+ T cells, which broadly impact T cell functions. T cell specific deletion of the YAP gene was shown to result in the increased activation and differentiation of T cells, which translated in vivo to an increased ability for T cells to block aggressive solid tumor growth. The concept of altering signals within immune cells to boost their ability to fight disease has come to the forefront of medical research, given the effectiveness that many immunotherapies have shown in the clinic. This study places YAP as a key effector of these disease-relevant immune modulating signals. Notably, the authors observed that deletion of YAP resulted in a greatly enhanced ability for T cells to infiltrate solid tumors and become locally activated within the tumor microenvironment. These observations may have important clinical implications, since a major challenge for current immunotherapies is a failure for T cells to effectively infiltrate solid tumors. This study also raises questions about the role of YAP and related signals, such as those mediated by the Hippo signaling pathway, in general T cell biology, opening the door to interesting future research directions.