Pluto Bioinformatics

GSE105439: Effects of the novel PI3K / inhibitor RP6530 on global gene expression in Hodgkin Lymphoma cell lines.

Bulk RNA sequencing

Tumor-associated macrophages (TAMs) are involved in the pathogenesis of Hodgkin lymphoma (HL) and correlate with negative prognosis. The phosphatidylinositol 3-kinase (PI3K) mediates tumor and endothelial cell survival, and macrophage activation. As PI3K and PI3K are constitutively activated in HL, we describe RP6530, a novel PI3K/ inhibitor, in clinical development for HL and NHL. RP6530 exhibits anti-proliferative and cytotoxic activity both in vitro in HL cell lines and in vivo in HL xenograft mouse models. By inhibiting the metabolic regulator Pyruvate Kinase M2 (PKM2), RP6530 downregulates lactic acid metabolism in HL cells switching the activation of macrophages from an immunosuppressive M2-like phenotype to a more inflammatory M1-like state. RP6530 reshapes the tumor microenvironment (TME), through the re-polarization of TAMs into pro-inflammatory macrophages and the inhibition of tumor vasculature. These data demonstrate the central role of PI3K / inhibition for targeting HL cells and TME, indicating RP6530 as a novel therapeutic opportunity for HL patients. SOURCE: Simone Serio ( - Humanitas Research Hospital

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