Gorini Francesca, Miceli Marco, de Antonellis Pasqualino, Amente Stefano, Zollo Massimo, Ferrucci Veronica
Department of Molecular Medicine and Medical Biotechnology (DMMBM), University of Naples, Naples, Italy.
CEINGE Biotecnologie Avanzate "Franco Salvatore", Naples, Italy.
Front Genet. 2023 Mar 10;14:1135404. doi: 10.3389/fgene.2023.1135404. eCollection 2023.
Medulloblastoma (MB) is a highly malignant childhood tumor of the cerebellum. Transcriptional and epigenetic signatures have classified MB into four molecular subgroups, further stratified into biologically different subtypes with distinct somatic copy-number aberrations, driver genes, epigenetic alterations, activated pathways, and clinical outcomes. The brain tumor microenvironment (BTME) is of importance to regulate a complex network of cells, including immune cells, involved in cancer progression in brain malignancies. MB was considered with a "cold" immunophenotype due to the low influx of immune cells across the blood brain barrier (BBB). Recently, this assumption has been reconsidered because of the identification of infiltrating immune cells showing immunosuppressive phenotypes in the BTME of MB tumors. Here, we are providing a comprehensive overview of the current status of epigenetics alterations occurring during cancer progression with a description of the genomic landscape of MB by focusing on immune cells within the BTME. We further describe how new immunotherapeutic approaches could influence concurring epigenetic mechanisms of the immunosuppressive cells in BTME. In conclusion, the modulation of these molecular genetic complexes in BTME during cancer progression might enhance the therapeutic benefit, thus firing new weapons to fight MB.
髓母细胞瘤(MB)是一种高度恶性的儿童小脑肿瘤。转录和表观遗传特征已将MB分为四个分子亚组,进一步细分为具有不同体细胞拷贝数畸变、驱动基因、表观遗传改变、激活途径和临床结果的生物学不同亚型。脑肿瘤微环境(BTME)对于调节包括免疫细胞在内的参与脑恶性肿瘤癌症进展的复杂细胞网络至关重要。由于免疫细胞穿过血脑屏障(BBB)的流入量低,MB被认为具有“冷”免疫表型。最近,由于在MB肿瘤的BTME中发现了显示免疫抑制表型的浸润免疫细胞,这一假设已被重新考虑。在这里,我们通过关注BTME内的免疫细胞,全面概述了癌症进展过程中发生的表观遗传改变的现状,并描述了MB的基因组格局。我们进一步描述了新的免疫治疗方法如何影响BTME中免疫抑制细胞的并发表观遗传机制。总之,在癌症进展过程中对BTME中的这些分子遗传复合物进行调节可能会增强治疗效果,从而为对抗MB提供新的武器。