Project description:Lenvatinib is an effective drug in advanced hepatocellular carcinoma (HCC). Its combination with the anti-PD1 immune checkpoint inhibitor pembrolizumab has achieved encouraging results in phase Ib and is currently being tested in phase III trials. Here, we aimed at exploring the molecular and immunomodulatory effects of lenvatinib alone or in combination with anti-PD1. We generated a syngeneic model of HCC in C57BL/6J mice and randomized the animals to receive placebo, lenvatinib, anti-PD1 or combination treatment. Transcriptomic analysis were performed to assess the expression profile of tumors from mice receiving each treatment strategy.
Project description:We used CRISPR/Cas9-mediated knockout of PRC2 core components, Eed and generated PRC2-isogenic murine mammary tumor model (AT3, sgCon vs. sgEed ) amenable for syngeneic transplant in C57BL/6J mice. Transcriptome analysis of the explanted PRC2-wt (sgCon) and PRC2-loss (sgEed) AT3 tumors by RNA-seq demonstrated that PRC2 loss led to the upregulation of various developmental pathways, and the downregulation of both innate and adaptive immune response pathways.