Schwarzlmueller Paul, Triebig Alexandra, Assié Guillaume, Jouinot Anne, Theurich Sebastian, Maier Tanja, Beuschlein Felix, Kobold Sebastian, Kroiss Matthias
Department of Medicine IV, LMU University Hospital, LMU Munich, Munich, Germany.
Université Paris Cité, CNRS, INSERM, Institut Cochin, Paris, France.
Nat Rev Endocrinol. 2025 Jun;21(6):331-343. doi: 10.1038/s41574-025-01102-2. Epub 2025 Mar 24.
Immune evasion is a hallmark of cancer progression but the role of steroid hormones in this evasion has long been underrated. This oversight is particularly notable for glucocorticoids given that exogenous glucocorticoids remain a cornerstone therapy in various oncological treatment regimens, supportive care and treatment of immune-related adverse events caused by immune-checkpoint inhibitors. Cortisol, the main endogenous glucocorticoid in humans, is secreted by the adrenal cortex in response to stress. Additionally, cortisol and its inactive metabolite cortisone can be interconverted to further modulate tissue-dependent glucocorticoid action. In the past 5 years, intratumoural production of glucocorticoids, by both immune and tumour cells, has been shown to support tumour immune evasion. Here, we summarize current progress at the crossroads of endocrinology and immuno-oncology. We outline the known effects of steroid hormones on different immune cell types with a focus on glucocorticoids and androgens. We conclude with options for pharmaceutical intervention, including the engineering of cell-based therapies that resist the immunosuppressive action of steroid hormones. Overall, local steroid production and metabolism are emerging elements of tumour immune suppression that are potentially amenable to therapeutic intervention. Targeting steroid hormones to enhance anticancer therapies could increase their efficacy but will require expertise in endocrine care.
免疫逃逸是癌症进展的一个标志，但类固醇激素在这种逃逸中的作用长期以来一直被低估。鉴于外源性糖皮质激素仍然是各种肿瘤治疗方案、支持性护理以及免疫检查点抑制剂引起的免疫相关不良事件治疗的基石，这种忽视在糖皮质激素方面尤为明显。皮质醇是人类主要的内源性糖皮质激素，由肾上腺皮质在应激反应时分泌。此外，皮质醇及其无活性代谢产物可的松可以相互转化，以进一步调节组织依赖性糖皮质激素的作用。在过去5年中，免疫细胞和肿瘤细胞在肿瘤内产生糖皮质激素已被证明有助于肿瘤免疫逃逸。在此，我们总结内分泌学和免疫肿瘤学交叉领域的当前进展。我们概述了类固醇激素对不同免疫细胞类型的已知影响，重点是糖皮质激素和雄激素。我们最后提出了药物干预的选择，包括设计能够抵抗类固醇激素免疫抑制作用的细胞疗法。总体而言，局部类固醇的产生和代谢是肿瘤免疫抑制的新出现的因素，可能适合进行治疗干预。靶向类固醇激素以增强抗癌治疗可能会提高其疗效，但需要内分泌护理方面的专业知识。
