Researchers explore potential new target for cancer immunotherapy

By Dr. Liji Thomas, MDFeb 27 2023Reviewed by Aimee Molineux *Important notice: bioRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Introduction ICB showed immense promise that has been only partly fulfilled because of its restricted response in a few tumor types and subsets of patients. This has driven intensive research into how tumors respond to ICB depending on their innate mechanisms. Meanwhile, earlier research has shown the crucial regulatory function played by the Hippo pathway in tumor development in mammalian organisms. One of the components of this pathway is the YAP downstream effector molecule, which is a coactivator during the transcription of various genes. It must bind to transcriptional factors such as TEAD-1-4.

What did the study show? The researchers knocked down the YAP gene in cancer cell lines and used these cells to cause cancers in two sets of mice: one immunodeficient and one immunocompetent. Both showed a reduction in tumor growth, by 40% and 60%, respectively. This indicates that YAP regulates the immune microenvironment and thus affects tumor development.

Thus, the level of YAP expression was inversely associated with NLCR5 expression and with APM expression. In other words, NLCR5 is a target gene of YAP/TEAD, and undergoes direct repression when bound by the latter. The end result is the inhibition of MHC-I APM expression via NLCR5.

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