{
  "abstract": "Sex differences in immune responses impact cancer outcomes and treatment response, including in glioblastoma (GBM). However, host factors underlying sex specific immune-cancer interactions are poorly understood. Here, we identify the neurotransmitter γ-aminobutyric acid (GABA) as a driver of GBM-promoting immune response in females. We demonstrated that GABA receptor B (GABBR) signaling enhances L-Arginine metabolism and nitric oxide synthase 2 (NOS2) expression in female granulocytic myeloid-derived suppressor cells (gMDSCs). GABBR agonist and GABA analog promoted GBM growth in females in an immune-dependent manner, while GABBR inhibition reduces gMDSC NOS2 production and extends survival only in females. Furthermore, female GBM patients have enriched GABA transcriptional signatures compared to males, and the use of GABA analogs in GBM patients is associated with worse short-term outcomes only in females. Collectively, these results highlight that GABA modulates anti-tumor immune response in a sex-specific manner, supporting future assessment of GABA pathway inhibitors as part of immunotherapy approaches.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Molecular and Cellular Pharmacology, Leonard M. Miller School of Medicine, University of Miami, Miami, FL, USA",
    "Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL, USA",
    "Department of Radiation Oncology, University of Michigan, Ann Arbor, MI, USA",
    "Rogel Cancer Center, University of Michigan, Ann Arbor, MI, USA",
    "Genomic Medicine Institute, Cleveland Clinic Research, Cleveland Clinic, Cleveland, OH, USA",
    "Leonard M. Miller School of Medicine, University of Miami, Miami, FL, USA",
    "Medical Oncology, Leonard M. Miller School of Medicine, University of Miami, Miami, FL, USA",
    "Department of Radiation Oncology, Leonard M. Miller School of Medicine, University of Miami, Miami, FL, USA",
    "Department of Pathology and Laboratory Medicine, Leonard M. Miller School of Medicine, University of Miami, Miami, FL, USA",
    "Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI, USA",
    "Department of Cancer Sciences, Cleveland Clinic Research, Cleveland, OH, USA",
    "Department of Surgery, Leonard M. Miller School of Medicine, University of Miami, Miami, FL, USA",
    "Vanderbilt University Medical Center, Nashville, TN, USA",
    "Center for Translational Science, Florida International University, Port St. Lucie, FL, USA",
    "Department of Cellular and Molecular Medicine, Florida International University, Miami, FL, USA",
    "Department of Neurosurgery, Leonard M. Miller School of Medicine, University of Miami, Miami, FL, USA",
    "Case Comprehensive Cancer Center, Cleveland, OH, USA",
    "Rose Ella Burkhardt Brain Tumor & Neuro-Oncology Center, Cleveland Clinic, Cleveland, OH, USA",
    "Miami VA Healthcare System, Miami, FL, USA",
    "Department of Neurosurgery, University of Michigan, Ann Arbor, MI, USA",
    "Department of Molecular and Cellular Pharmacology, Leonard M. Miller School of Medicine, University of Miami, Miami, FL, USA. defne.bayik@miami.edu",
    "Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL, USA. defne.bayik@miami.edu"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 38,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Asmita Pathak",
      "orcid": "0009-0006-5955-1714"
    },
    {
      "affs": [
        2,
        3
      ],
      "name": "Sravya Palavalasa",
      "orcid": "0000-0001-5276-3972"
    },
    {
      "affs": [
        0
      ],
      "name": "Bruno Colon",
      "orcid": "0009-0006-7463-0111"
    },
    {
      "affs": [
        1
      ],
      "name": "Erika Ciervo",
      "orcid": "0009-0007-9351-368X"
    },
    {
      "affs": [
        4
      ],
      "name": "Yadi Zhou",
      "orcid": "0000-0002-6049-0545"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Oriana Teran Pumar",
      "orcid": "0000-0002-0536-9056"
    },
    {
      "affs": [
        0
      ],
      "name": "Brandon Emanuel León",
      "orcid": "0009-0002-1708-7563"
    },
    {
      "affs": [
        0,
        5
      ],
      "name": "Jonathan Mitchell"
    },
    {
      "affs": [
        6
      ],
      "name": "Pedro Henrique Assenza Tavares Coroa"
    },
    {
      "affs": [
        7
      ],
      "name": "Beatriz Mateo-Victoriano",
      "orcid": "0000-0003-3281-4933"
    },
    {
      "affs": [
        2,
        3
      ],
      "name": "Andrew J. Scott",
      "orcid": "0000-0002-0835-4888"
    },
    {
      "affs": [
        8
      ],
      "name": "Durga Prasad Gannamedi",
      "orcid": "0009-0008-4398-9118"
    },
    {
      "affs": [
        9
      ],
      "name": "Harrison K. A. Wong"
    },
    {
      "affs": [
        3
      ],
      "name": "Liping Zhang",
      "orcid": "0000-0002-1512-4853"
    },
    {
      "affs": [
        10
      ],
      "name": "Juyeun Lee",
      "orcid": "0000-0001-8276-5020"
    },
    {
      "affs": [
        10
      ],
      "name": "Kristen Kay",
      "orcid": "0009-0007-0428-7693"
    },
    {
      "affs": [
        1
      ],
      "name": "Efe Karaca",
      "orcid": "0000-0003-4109-6013"
    },
    {
      "affs": [
        10
      ],
      "name": "Diana H. Chin",
      "orcid": "0000-0002-1645-3552"
    },
    {
      "affs": [
        11
      ],
      "name": "Haleh Amirian",
      "orcid": "0000-0002-6094-1342"
    },
    {
      "affs": [
        6
      ],
      "name": "İrem Karaman",
      "orcid": "0000-0001-7559-9095"
    },
    {
      "affs": [
        0
      ],
      "name": "Preyasha Shrestha",
      "orcid": "0009-0001-5120-5925"
    },
    {
      "affs": [
        12
      ],
      "name": "Katelyn Sellick"
    },
    {
      "affs": [
        12
      ],
      "name": "E. Danielle Dean",
      "orcid": "0000-0002-7157-5683"
    },
    {
      "affs": [
        8,
        1
      ],
      "name": "Daniel Bilbao",
      "orcid": "0000-0003-1630-8811"
    },
    {
      "affs": [
        11,
        1
      ],
      "name": "Jashodeep Datta",
      "orcid": "0000-0003-2869-1571"
    },
    {
      "affs": [
        7,
        1
      ],
      "name": "Scott M. Welford",
      "orcid": "0000-0002-9579-4223"
    },
    {
      "affs": [
        13,
        14
      ],
      "name": "María Clara Franco",
      "orcid": "0000-0002-7971-9805"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Kiran Kurmi",
      "orcid": "0000-0002-1345-0196"
    },
    {
      "affs": [
        15,
        1
      ],
      "name": "Ashish Harish Shah",
      "orcid": "0000-0002-0183-1274"
    },
    {
      "affs": [
        16,
        4
      ],
      "name": "Feixiong Cheng",
      "orcid": "0000-0002-1736-2847"
    },
    {
      "affs": [
        16,
        10,
        17
      ],
      "name": "Justin Durla Lathia",
      "orcid": "0000-0003-3168-7290"
    },
    {
      "affs": [
        7,
        1
      ],
      "name": "Priyamvada Rai",
      "orcid": "0000-0001-7822-7553"
    },
    {
      "affs": [
        8,
        18,
        1
      ],
      "name": "David B. Lombard",
      "orcid": "0000-0002-4292-0185"
    },
    {
      "affs": [
        9,
        3
      ],
      "name": "Costas Andreas Lyssiotis",
      "orcid": "0000-0001-9309-6141"
    },
    {
      "affs": [
        6,
        1
      ],
      "name": "Dionysios C. Watson"
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    {
      "affs": [
        1
      ],
      "name": "Michele Ceccarelli",
      "orcid": "0000-0002-4702-6617"
    },
    {
      "affs": [
        19,
        2,
        3
      ],
      "name": "Daniel Richard Wahl",
      "orcid": "0000-0001-9894-5085"
    },
    {
      "affs": [
        20,
        21
      ],
      "name": "Defne Bayık",
      "orcid": "0000-0002-4740-8869"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/4nb2kwnxengjz.bib",
  "cited_by": 12,
  "doi": "10.1038/s43018-026-01192-5",
  "fulltext_url": null,
  "id": "4nb2kwnxengjz",
  "issns": [
    "2662-1347"
  ],
  "landing_url": "https://doi.org/10.1038/s43018-026-01192-5",
  "language": "en",
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2403|Immune cells in cancer"
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  "pdf_url": "https://www.nature.com/articles/s43018-026-01192-5.pdf",
  "pmcid": "PMC13400302",
  "pmid": "42337052",
  "published": "2026-06-23",
  "publisher": "Nature Portfolio",
  "ris": "https://research.draconitic.com/paper/4nb2kwnxengjz.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T13:26:51Z",
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      "url": "https://doi.org/10.1038/s43018-026-01192-5"
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  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:2403|Immune cells in cancer",
      "subfield": "immunology"
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  "title": "GABA signaling activation drives glioblastoma progression in female mice through myeloid-derived suppressor cells",
  "title_text": "GABA signaling activation drives glioblastoma progression in female mice through myeloid-derived suppressor cells",
  "type": "peer-reviewed",
  "updated_at": "2026-11-09T13:21:11Z",
  "url": "https://research.draconitic.com/paper/4nb2kwnxengjz",
  "venue": "Nature Cancer",
  "versions": []
}