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Spatial organization of purinergic signaling in glioma suggests immunotherapy target

Sandro Santagata

A team co-led by Ludwig Harvard investigator Sandro Santagata reported in Nature Communications in August the findings from a study integrating a system for multiplexed tissue imaging developed at the Harvard Center and single-cell RNA-sequencing to explore the spatial organization and significance of purinergic signaling in high-grade gliomas (HGGs). Extracellular purinergic signaling involves the breakdown of ATP into adenosine, which is an important regulator of the tumor microenvironment and anti-tumor immune responses. CD39, an enzyme expressed by immune cells, and CD73, an enzyme expressed on cancer cells, cooperate to generate adenosine. Sandro and his colleagues found that CD73 levels in HGGs correlate with the differentiation state of tumor cells and the cancer-fueling amplification of EGFR. The spatial proximity of cancer cells expressing CD73 and immune cells expressing CD39 correlates with poor patient outcome in adult glioblastoma. Though pediatric high-grade gliomas, including diffuse intrinsic pontine glioma (DIPG), harbor genetic drivers distinct from those in adults, they too feature elevated interaction between cancer cell CD73 and microglial CD39. These results suggest that inhibiting this signaling pathway could be an attractive immunotherapeutic strategy in both adult and pediatric HGGs, as well as other brain tumors.

Single cell spatial analysis reveals the topology of immunomodulatory purinergic signaling in glioblastoma
Nature Communications, 2022 August 16

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