Authors
Asmita Pathak, Palavalasa Sravya, Bruno Colon, Erika Ciervo, Yadi Zhou, Oriana Y Teran Pumar, Brandon Emanuel León, Jonathan Mitchell, Pedro Henrique Assenza Tavares Coroa, Beatriz Mateo-Victoriano, Andrew J Scott, Durga Prasad Gannamedi, Harrison K A Wong, Li Zhang, Juyeun Lee, Kristen Kay, Efe Karaca, Diana H Chin, Haleh Amirian, Irem Karaman, Preyasha Shrestha, Katelyn Sellick, Danielle Dean, Daniel Bilbao Cortes, Jashodeep Datta, Scott M Welford, Maria Clara Franco, Kiran Kurmi, Ashish H Shah, Feixiong Cheng, Justin D Lathia, Priyamvada Rai, David B Lombard, Costas A Lyssiotis, Dionysios C Watson, Michele Ceccarelli, Daniel R Wahl, Defne Bayik
Published in
Nature cancer. Jun 23, 2026. Epub Jun 23, 2026.
Abstract
Sex differences in immune responses impact cancer outcomes and treatment response, including in glioblastoma (GBM). However, host factors underlying distinct immune-cancer interactions are poorly understood. Here we identify γ-aminobutyric acid (GABA) as a female-specific driver of GBM-promoting immune response. We demonstrated that GABA receptor B (GABBR) signaling enhances the T cell suppressive function of granulocytic myeloid-derived suppressor cells (gMDSCs) from female mice by upregulating the cationic amino acid transporter 2-L-arginine-nitric oxide synthase 2 (NOS2) pathway. GABBR agonism promotes GBM growth in female preclinical models through gMDSCs, while GABBR antagonism extends survival and reduces NOS2 in tumor-infiltrating gMDSCs only in female mice. Immune cells from female participants with GBM have enriched GABA transcriptional signatures and a higher GABA concentration compared to male counterparts. Collectively, these results highlight the sex-specific immunomodulatory role of GABA in tumorigenesis, supporting future assessment of GABA pathway inhibitors for cancer immunotherapy.
PMID:
42337052
Bibliographic data and abstract were imported from PubMed on 24 Jun 2026.
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