Abstract
Glioblastoma (GBM), the most common primary malignant brain tumor, remains difficult to treat and shares phenotypes, including an aberrant immune response, with other neurological disorders. Understanding the cellular and molecular mechanisms underlying this pathological immune response remains a priority, particularly as standard of care for advanced cancers evolves to include immunotherapies, which have yet to show strong clinical efficacy in GBM. Epidemiological evidence supports a sex difference in GBM, with increased prevalence in males, and recent studies identified differences between males and females ranging from genetic aberrations to cellular programs. Sex differences have also been identified in immune response, and in this mini-review, we present these differences to highlight potential sex-specific cellular and molecular mechanisms that underly GBM growth and response to immunotherapies. These sex differences offer an opportunity to understand GBM pathogenesis and extend beyond GBM to other tumors and neurological disorders to inform the development of next-generation therapies.
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Acknowledgements
We would like to thank the members of the Lathia laboratory for insightful discussions. We also thank the members of the Consortium on Sex Differences in Cancer (COSINE, https://cosineconsortium.org/), including Drs. Jill Barnholtz-Sloan (Case Western Reserve University), Josh Rubin (Washington University in St. Louis), James Connor (Penn State College of Medicine), and Michael Berens (TGEN), for ongoing, engaging discussions. We thank Ms. Amanda Mendelsohn for illustration assistance, Dr. Erin Mulkearns-Hubert for editorial assistance, and Dr. Defne Bayik for critical feedback on this manuscript. Work on sex differences in the Lathia laboratory is supported by the Cleveland Clinic, Case Comprehensive Cancer Center, the American Brain Tumor Association and NIH R01 NS109742 and P01 CA245705.
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Work on sex differences in the Lathia laboratory is supported by the Cleveland Clinic, Case Comprehensive Cancer Center, the American Brain Tumor Association and NIH R01 NS109742 and P01 CA245705.
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Conception and design (JL, KK, KT, MSA, JDL), Literature search (JL, KK, KT), Manuscript preparation (JL, KK, KT, MSA, JDL), Final approval (JL, KK, KT, MSA, JDL).
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Lee, J., Kay, K., Troike, K. et al. Sex Differences in Glioblastoma Immunotherapy Response. Neuromol Med 24, 50–55 (2022). https://doi.org/10.1007/s12017-021-08659-x
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DOI: https://doi.org/10.1007/s12017-021-08659-x