Targeting the hippo pathway as a potential regulator of immune checkpoints in cancer immunotherapy

The Hippo pathway is a conserved signaling cascade in mammals, known for its critical role in regulating cellular functions, including cell growth, differentiation, and organ size. These functions are largely mediated by the transcriptional effectors YAP and TAZ, which regulate gene expression through interactions with TEAD family transcription factors. Aberrant Hippo pathway signaling has been implicated in various aspects of cancer progression, including tumorigenesis, invasion and metastasis. This review explores the Hippo pathway has been implicated in the regulation of immune checkpoint (IC) expression and the role of the Hippo pathway in the tumor microenvironment (TME). Specifically, the Hippo pathway regulates the TME by influencing T-cell function, myeloid-derived suppressor cell (MDSC) activity, and macrophage polarization and recruitment. Furthermore, we also discuss how the Hippo pathway regulates immune checkpoint inhibitors (ICIs) and its potential for enhancing immunotherapy efficacy while reducing associated adverse effects.