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The inactive X chromosome drives sex differences in microglial inflammatory activity in human glioblastoma.
Tharp, Marla E; Han, Claudia Z; Balak, Chris D; Fitzpatrick, Conor; O'Connor, Carolyn; Preissl, Sebastian; Buchanan, Justin; Nott, Alexi; Escoubet, Laure; Mavrommatis, Konstantinos; Gupta, Mihir; Schwartz, Marc S; Sang, U Hoi; Jones, Pamela S; Levy, Michael L; Gonda, David D; Ben-Haim, Sharona; Ciacci, Joseph; Barba, David; Khalessi, Alexander; Coufal, Nicole G; Chen, Clark C; Glass, Christopher K; Page, David C.
Affiliation
  • Tharp ME; Whitehead Institute, Cambridge, MA 02142, USA.
  • Han CZ; These authors contributed equally.
  • Balak CD; Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
  • Fitzpatrick C; These authors contributed equally.
  • O'Connor C; Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
  • Preissl S; Flow Cytometry Core Facility, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
  • Buchanan J; Flow Cytometry Core Facility, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
  • Nott A; Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
  • Escoubet L; Center for Epigenomics, University of California, San Diego, La Jolla, CA 92093, USA.
  • Mavrommatis K; Present address: Institute of Experimental and Clinical Pharmacology and Toxicology, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
  • Gupta M; Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
  • Schwartz MS; Center for Epigenomics, University of California, San Diego, La Jolla, CA 92093, USA.
  • Sang UH; Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
  • Jones PS; Department of Brain Sciences, Imperial College London, London, United Kingdom.
  • Levy ML; UK Dementia Research Institute, Imperial College London, London, United Kingdom.
  • Gonda DD; Bristol-Myers Squibb, San Diego, CA 92121, USA.
  • Ben-Haim S; Bristol-Myers Squibb, San Francisco, CA 94158 USA.
  • Ciacci J; Department of Neurosurgery, University of California, San Diego, La Jolla, CA 92037, USA.
  • Barba D; Present address: Department of Neurosurgery, Yale University, New Haven, CT 06520, USA.
  • Khalessi A; Department of Neurosurgery, University of California, San Diego, La Jolla, CA 92037, USA.
  • Coufal NG; Department of Neurosurgery, University of California, San Diego, La Jolla, CA 92037, USA.
  • Chen CC; Department of Neurosurgery, University of California, San Diego, La Jolla, CA 92037, USA.
  • Glass CK; Present address: Department of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
  • Page DC; Department of Neurosurgery, University of California, San Diego-Rady Children's Hospital, San Diego, CA 92123, USA.
bioRxiv ; 2024 Jun 06.
Article in En | MEDLINE | ID: mdl-38895459
ABSTRACT
Biological sex is an important risk factor in cancer, but the underlying cell types and mechanisms remain obscure. Since tumor development is regulated by the immune system, we hypothesize that sex-biased immune interactions underpin sex differences in cancer. The male-biased glioblastoma multiforme (GBM) is an aggressive and treatment-refractory tumor in urgent need of more innovative approaches, such as considering sex differences, to improve outcomes. GBM arises in the specialized brain immune environment dominated by microglia, so we explored sex differences in this immune cell type. We isolated adult human TAM-MGs (tumor-associated macrophages enriched for microglia) and control microglia and found sex-biased inflammatory signatures in GBM and lower-grade tumors associated with pro-tumorigenic activity in males and anti-tumorigenic activity in females. We demonstrated that genes expressed or modulated by the inactive X chromosome facilitate this bias. Together, our results implicate TAM-MGs, specifically their sex chromosomes, as drivers of male bias in GBM.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Language: En Journal: BioRxiv Year: 2024 Type: Article Affiliation country: United States
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PubMed Links
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Full text: 1 Collection: 01-internacional Database: MEDLINE Language: En Journal: BioRxiv Year: 2024 Type: Article Affiliation country: United States