Glioblastoma (GBM) constitutes the most lethal primary brain tumor for which immunotherapy has provided limited benefit. The unique brain immune landscape is reflected in a complex tumor immune microenvironment (TIME) in GBM. Here, single cell sequencing of the GBM TIME revealed that microglia were under severe oxidative stress, which induced nuclear receptor subfamily 4 group A member 2 (NR4A2)-dependent transcriptional activity in microglia. Heterozygous Nr4a2 (Nr4a2+/-) or microglia-specific Nr4a2 (Nr4a2fl/flCx3cr1cre) genetic targeting reshaped microglia plasticity in vivo by reducing alternatively activated microglia and enhancing antigen presentation capacity for CD8+ T cells in GBM. In microglia, NR4A2 activated squalene monooxygenase (SQLE) to dysregulate cholesterol homeostasis. Pharmacological NR4A2 inhibition attenuated the pro-tumorigenic TIME, and targeting the NR4A2 or SQLE enhanced therapeutic efficacy of immune checkpoint blockade in vivo. Collectively, oxidative stress promotes tumor growth through NR4A2-SQLE activity in microglia, informing novel immune therapy paradigms in brain cancer.
Pharmacology, Toxicology and Pharmaceutical Science
1
3%
Other
2
5%
Unknown
23
57%
Attention Score in Context
Attention Score in Context
This research output has an Altmetric Attention Score of 21. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 09 May 2023.
All research outputs
#2,285,197
of 34,632,158 outputs
Outputs from Cancer Discovery
#1,060
of 4,800 outputs
Outputs of similar age
#40,180
of 530,382 outputs
Outputs of similar age from Cancer Discovery
#24
of 92 outputs
Altmetric has tracked 34,632,158 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 93rd percentile: it's in the top 10% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 4,800 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 24.7. This one has done well, scoring higher than 77% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 530,382 tracked outputs that were published within six weeks on either side of this one in any source. This one has done particularly well, scoring higher than 92% of its contemporaries.
We're also able to compare this research output to 92 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 73% of its contemporaries.
