Abstract B16: Silence of Hippo pathway induces protumoral immunity: New therapeutic target of glioblastomas

Abstract

Abstract The Hippo pathway plays a critical role in various cancers, but its role in glioblastoma (GBM) has not been properly addressed. To assess the clinical relevance of the Hippo pathway in GBM, we generated a core gene expression signature reflecting silence of the Hippo pathway (SOH), and validated it in GBM patient samples from The Cancer Genome Atlas (TCGA) and in a separate cohort, revealing that SOH signature was associated with poor prognosis in GBM in both cohorts. Expression levels of CTGF and CYR61, the most reliable and well-known downstream targets of YAP1 (a target of the Hippo pathway), were markedly increased in GBM with the SOH signature. GBM showing the SOH signature was associated with an increased Immune signature score (ISS), suggesting that these patients might be good potential candidates for immunotherapy. Genes differentially expressed between samples with the SOH signature and samples with an active Hippo signature showed that many inhibitory immune checkpoint genes, such as CTLA4, PD-1, and PD-L2, were upregulated in the SOH subgroup, suggesting that YAP1/TAZ may induce resistance of cancer cells to host immune response in GBM. Also, many M2-polarized microglial markers and innate immune pathways were activated in the SOH subgroup. The SOH signature was strongly correlated with the TGF-β signature, which was also associated with a high ISS and mesenchymal features. In summary, SOH induces protumoral immunity in various ways, which may be new immunotherapeutic targets of GBM. Note: This abstract was not presented at the conference. Citation Format: Eui Hyun Kim, Seok-Gu Kang, Ju-Seog Lee. Silence of Hippo pathway induces protumoral immunity: New therapeutic target of glioblastomas [abstract]. In: Proceedings of the AACR Special Conference on the Hippo Pathway: Signaling, Cancer, and Beyond; 2019 May 8-11; San Diego, CA. Philadelphia (PA): AACR; Mol Cancer Res 2020;18(8_Suppl):Abstract nr B16.