Department of Cardiovascular & Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, USA.
Department of Molecular Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, USA.
Neuromolecular Med. 2022 Mar;24(1):50-55. doi: 10.1007/s12017-021-08659-x. Epub 2021 Apr 17.
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.
胶质母细胞瘤（GBM）是最常见的原发性恶性脑肿瘤，目前仍然难以治疗，并且与其他神经疾病具有相似的表型，包括异常的免疫反应。了解这种病理性免疫反应的细胞和分子机制仍然是当务之急，特别是随着癌症的标准治疗方法演变为包括免疫疗法，而免疫疗法在 GBM 中尚未显示出强大的临床疗效。流行病学证据支持 GBM 存在性别差异，男性的发病率更高，最近的研究发现男性和女性之间存在从遗传异常到细胞程序的差异。免疫反应中也存在性别差异，在这篇迷你综述中，我们提出了这些差异，以强调潜在的性别特异性细胞和分子机制，这些机制是 GBM 生长和对免疫疗法反应的基础。这些性别差异为了解 GBM 的发病机制提供了机会，并超越 GBM 扩展到其他肿瘤和神经疾病，为下一代治疗方法的发展提供信息。
