Hippo signaling as a therapeutic switch for T cell functions and tumor immunity

The Hippo signaling pathway is a fundamental regulator of organ growth, tissue regeneration, and cellular homeostasis, with far-reaching implications in cancer biology and immunology. Dysregulation of this pathway, particularly through its downstream effectors YAP (Yes-associated protein) and TAZ (transcriptional co-activator with PDZ-binding motif), is closely associated with oncogenic transformation and the establishment of an immunosuppressive tumor microenvironment (TME). This review discusses current knowledge on the multifaceted roles of Hippo signaling in cancer, focusing on its interactions with T cell-mediated immunity and mechanisms of tumor immune regulation. Aberrant YAP/TAZ activation enhances cancer cell proliferation, remodels the TME, and reprograms immune responses to favor tumor growth and immune evasion. The review explores how modulation of Hippo pathway components influences both tumor progression and immune cell function, highlighting its central role in shaping anti-tumor immunity. Furthermore, the therapeutic potential of targeting YAP/TAZ signaling is discussed in the context of advancing precision medicine and improving immunotherapeutic outcomes. Collectively, this work highlights the Hippo signaling cascade as both a key driver of tumorigenesis and a crucial regulator of immune modulation. A comprehensive understanding of its molecular interactions with T cells and the TME will support the development of innovative YAP/TAZ-targeted strategies that integrate molecular signaling and immune modulation, offering new directions for effective cancer therapy.