Department of Medical Biotechnologies and Translational Medicine, University of Milan, Milan, Italy.
Laboratory of Clinical and Experimental Immunology, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy.
Front Immunol. 2023 Jan 10;13:1074762. doi: 10.3389/fimmu.2022.1074762. eCollection 2022.
INTRODUCTION: Adult-type diffuse gliomas are malignant primary brain tumors characterized by very poor prognosis. Dendritic cells (DCs) are key in priming antitumor effector functions in cancer, but their role in gliomas remains poorly understood. METHODS: In this study, we characterized tumor-infiltrating DCs (TIDCs) in adult patients with newly diagnosed diffuse gliomas by using multi-parametric flow cytometry and single-cell RNA sequencing. RESULTS: We demonstrated that different subsets of DCs are present in the glioma microenvironment, whereas they are absent in cancer-free brain parenchyma. The largest cluster of TIDCs was characterized by a transcriptomic profile suggestive of severe functional impairment. Patients undergoing perioperative corticosteroid treatment showed a significant reduction of conventional DC1s, the DC subset with key functions in antitumor immunity. They also showed phenotypic and transcriptional evidence of a more severe functional impairment of TIDCs. DISCUSSION: Overall, the results of this study indicate that functionally impaired DCs are recruited in the glioma microenvironment. They are severely affected by dexamethasone administration, suggesting that the detrimental effects of corticosteroids on DCs may represent one of the mechanisms contributing to the already reported negative prognostic impact of steroids on glioma patient survival.
简介:成人型弥漫性神经胶质瘤是恶性原发性脑肿瘤,其预后极差。树突状细胞(DCs)在引发癌症中的抗肿瘤效应功能方面起着关键作用,但它们在神经胶质瘤中的作用仍知之甚少。
方法:在这项研究中,我们通过多参数流式细胞术和单细胞 RNA 测序对新诊断的弥漫性神经胶质瘤成人患者中的肿瘤浸润树突状细胞(TIDCs)进行了特征描述。
结果:我们证明了不同亚群的 DC 存在于神经胶质瘤微环境中,而在无癌的脑实质中不存在。TIDCs 的最大簇表现出提示严重功能障碍的转录组特征。接受围手术期皮质类固醇治疗的患者表现出常规 DC1s 的显著减少,而 DC1s 是抗肿瘤免疫中的关键功能亚群。它们还表现出 TIDCs 更严重的功能障碍的表型和转录证据。
讨论:总的来说,这项研究的结果表明,功能受损的 DC 被募集到神经胶质瘤微环境中。它们受到地塞米松给药的严重影响,这表明皮质类固醇对 DC 的有害影响可能是类固醇对神经胶质瘤患者生存的已有报道的负面预后影响的机制之一。
Front Immunol. 2023
Int J Cancer. 2013-9-4
Am J Pathol. 2012-7-13
Neurooncol Pract. 2025-1-31
Cancers (Basel). 2023-5-25
Sci Immunol. 2022-4
Neuro Oncol. 2021-8-2
Lancet. 2021-3-13
Front Pharmacol. 2020-6-30