Poggi Alessandro, Reggiani Francesco, Azevedo Helena S, Raffaghello Lizzia, Pereira Rui Cruz
Molecular Oncology and Angiogenesis Unit, IRCCS Ospedale Policlinico San Martino, Genoa, Italy.
Gene Expression Regulation Unit, IRCCS Ospedale Policlinico San Martino, Genoa, Italy.
Front Immunol. 2025 Jul 3;16:1602930. doi: 10.3389/fimmu.2025.1602930. eCollection 2025.
Medulloblastoma is an aggressive central nervous system tumor affecting children more commonly between the ages of 5-9. It is usually localized in the cerebellum, leading to diffusion of tumor cells through the cerebrospinal fluid and metastases to other portions of the brain and spinal cord. Conventional treatment consists of surgical resection followed by adjuvant radiation and/or chemotherapy. The side effects of these therapies are critical to consider, especially given that patients are in a distinct stage of their lives. In addition, the overall survival is not satisfactory ranging from 50-90% depending on the type of medulloblastoma. The molecular characterization has broadly subdivided medulloblastoma into four subgroups, and more recently, the single-cell transcriptomics studies have further identified several other subgroups. Important advances have been reported on the cell origin, their plasticity, heterogeneity of genetic and epigenetic alteration, and interaction with the immune and stromal components of the tumor microenvironment. Research studies on these key points are essential to make advances in planning the application of conventional therapies together with immunotherapies. Herein, we discuss the main advances recently obtained on medulloblastoma biology and immunotherapies. Overall, the biological and molecular features of medulloblastoma are briefly summarized to understand the reason for the application of the old and new immunotherapies. Immunotherapies considered include the identification of potential medulloblastoma neoantigens and tumor-associated antigens to generate antigen-specific T lymphocytes. The main antigens expressed by medulloblastoma cells and/or by components of the tumor microenvironment will be considered as the molecular targets of antibodies, antibody derivatives, and chimeric antigen receptor effector cells to improve the conventional therapies. In the last portion of this review, the brief analysis of the activating and inhibiting receptors expressed by antitumor T, natural killer, and unconventional T cells can give new insights into the potential treatment of medulloblastoma.
髓母细胞瘤是一种侵袭性中枢神经系统肿瘤,在5至9岁的儿童中更为常见。它通常位于小脑,导致肿瘤细胞通过脑脊液扩散并转移至脑和脊髓的其他部位。传统治疗包括手术切除,随后进行辅助放疗和/或化疗。考虑到患者正处于生命中的特殊阶段,这些治疗的副作用至关重要。此外,总体生存率并不令人满意,根据髓母细胞瘤的类型,生存率在50%至90%之间。分子特征已将髓母细胞瘤大致分为四个亚组,最近,单细胞转录组学研究进一步确定了其他几个亚组。在细胞起源、可塑性、基因和表观遗传改变的异质性以及与肿瘤微环境的免疫和基质成分的相互作用方面已报道了重要进展。对这些关键点的研究对于在规划传统疗法与免疫疗法联合应用方面取得进展至关重要。在此,我们讨论最近在髓母细胞瘤生物学和免疫疗法方面取得的主要进展。总体而言,简要总结髓母细胞瘤的生物学和分子特征,以理解应用新旧免疫疗法的原因。所考虑的免疫疗法包括识别潜在的髓母细胞瘤新抗原和肿瘤相关抗原,以产生抗原特异性T淋巴细胞。髓母细胞瘤细胞和/或肿瘤微环境成分表达的主要抗原将被视为抗体、抗体衍生物和嵌合抗原受体效应细胞的分子靶点,以改善传统疗法。在本综述的最后部分,对抗肿瘤T细胞、自然杀伤细胞和非常规T细胞表达的激活和抑制受体的简要分析可为髓母细胞瘤的潜在治疗提供新见解。
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