Sponsored by
This preclinical glioblastoma (GBM) study found that the neurotransmitter GABA acts directly on a type of immune cell called a granulocytic myeloid-derived suppressor cell (gMDSC), altering arginine metabolism and making these cells more effective at suppressing the body's anti-tumor immune response -- but only in females. Using female mouse models of GBM, the researchers showed that blocking GABA receptor signaling reduced this immunosuppressive activity and improved outcomes, while having no effect in males, suggesting that GABA signaling may represent a female-specific immunotherapy target. Although GABA is best known as a neurotransmitter in the brain, this study highlights a previously underappreciated role for GABA signaling in regulating immune cells within the tumor microenvironment.
This sex-specific signaling difference identified in mice was also supported by analyses of multiple independent human datasets and patient tumor samples, substantially increasing confidence that these findings are relevant to human GBM, although it remains unknown whether blocking GABA receptor signaling will improve outcomes for women with GBM.