Abstract At present there is a lack of effective treatments for pediatric High-Grade Glioma (pHGG). While conventional immunotherapies have been effective in treating cancers in less privileged spaces, they have been largely unsuccessful in CNS malignancies. Research conducted primarily on adult brain tumors has demonstrated the importance of immunoediting and the tumor microenvironment (TME) in both preventing progression of disease and tumor escape however, the pediatric space is largely unexplored. Building on this understanding, our research aims to further explore the interaction of pHGG and the innate immune system with the goal of harnessing anti-tumor activity in the TME utilizing immunotherapy. The growing body of knowledge about pHGG demonstrates important differences compared to adult Glioblastoma (GBM) extending beyond genomic mutational profiles. In this study, we investigated expression of the immunostimulatory STING signaling pathway in pHGG cells, as well as the immunology target GD2 ganglioside. Here, we demonstrate that STING pathway components are expressed in pHGG cells, and that treatment of cells with the STING agonist ADU-S100 results in robust downstream signaling resulting in type I interferon secretion and increased cytotoxic activity of peripheral blood mononuclear cells (PBMCs) in co-culture assays. Furthermore, our research demonstrates robust expression of GD2 in pHGG cell lines. Delivery of an anti-GD2 monoclonal antibody, Dinutuximab, to these tumors appears to activate the anti-tumor effects of PBMCs. These findings highlight promising therapeutic avenues for pHGG emphasizing the potential of targeted immunotherapies. Studies evaluating the effects of STING agonists in combination with Dinutuximab are currently ongoing in co-cultures and in murine models of pHGG.
Hawkins et al. (Fri,) studied this question.
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