{Reference Type}: Journal Article
{Title}: Hippo-signaling-controlled MHC class I antigen processing and presentation pathway potentiates antitumor immunity.
{Author}: Peng L;Zhou L;Li H;Zhang X;Li S;Wang K;Yang M;Ma X;Zhang D;Xiang S;Duan Y;Wang T;Sun C;Wang C;Lu D;Qian M;Wang Z;
{Journal}: Cell Rep
{Volume}: 43
{Issue}: 4
{Year}: 2024 Apr 23
暂无{DOI}: 10.1016/j.celrep.2024.114003
{Abstract}: The major histocompatibility complex class I (MHC class I)-mediated tumor antigen processing and presentation (APP) pathway is essential for the recruitment and activation of cytotoxic CD8+ T lymphocytes (CD8+ CTLs). However, this pathway is frequently dysregulated in many cancers, thus leading to a failure of immunotherapy. Here, we report that activation of the tumor-intrinsic Hippo pathway positively correlates with the expression of MHC class I APP genes and the abundance of CD8+ CTLs in mouse tumors and patients. Blocking the Hippo pathway effector Yes-associated protein/transcriptional enhanced associate domain (YAP/TEAD) potently improves antitumor immunity. Mechanistically, the YAP/TEAD complex cooperates with the nucleosome remodeling and deacetylase complex to repress NLRC5 transcription. The upregulation of NLRC5 by YAP/TEAD depletion or pharmacological inhibition increases the expression of MHC class I APP genes and enhances CD8+ CTL-mediated killing of cancer cells. Collectively, our results suggest a crucial tumor-promoting function of YAP depending on NLRC5 to impair the MHC class I APP pathway and provide a rationale for inhibiting YAP activity in immunotherapy for cancer.