目前髓母细胞瘤的护理治疗标准不足，因为这些治疗没有考虑肿瘤异质性。需要更新、更安全、针对患者的治疗方法来治疗标准疗法无法治愈的高危髓母细胞瘤患者。免疫疗法是一种有前途的治疗方式，可能是提高生存率和避免发病率的关键。为了有效的免疫反应，必须针对适当的肿瘤抗原。虽然先前已报道过具有亚组特异性基因替换的髓母细胞瘤患者，但这些基因改变的免疫原性仍然未知。本研究的目的是鉴定潜在的肿瘤排斥抗原，用于开发针对髓母细胞瘤的抗原导向细胞疗法。我们开发了癌症免疫基因组学流程，并对髓母细胞瘤亚组特异性转录谱进行了全面分析（n = 170, 18 WNT, 46 SHH、41 第 3 组和 65 第 4 组患者肿瘤）可通过国际癌症基因组联盟 (ICGC) 和欧洲基因组-表型档案 (EGA) 获取。我们对多种抗原类别进行了计算机抗原预测，包括新抗原、肿瘤相关抗原 (TAA) 和融合蛋白。此外，我们使用最新的计算解卷积方法评估了肿瘤细胞中的抗原加工和呈递途径以及免疫浸润细胞景观。发现髓母细胞瘤患者表达多种私有和共享的免疫原性抗原。对于所有分子亚群，预测的 TAA 比例均高于新抗原和基因融合，但声波刺猬 (SHH) 除外，其新抗原负担较高。重要的是，发现所有髓母细胞瘤亚组的大多数患者都表达癌症睾丸抗原以及以前未被重视的神经发育抗原。尽管免疫学上较冷，但髓母细胞瘤亚组被发现具有独特的免疫细胞基因特征。使用定制抗原预测管道，我们鉴定了潜在的肿瘤排斥抗原，对髓母细胞瘤免疫疗法的发展具有重要意义。© 2024。作者。

The current standard of care treatments for medulloblastoma are insufficient as these do not take tumor heterogeneity into account. Newer, safer, patient-specific treatment approaches are required to treat high-risk medulloblastoma patients who are not cured by the standard therapies. Immunotherapy is a promising treatment modality that could be key to improving survival and avoiding morbidity. For an effective immune response, appropriate tumor antigens must be targeted. While medulloblastoma patients with subgroup-specific genetic substitutions have been previously reported, the immunogenicity of these genetic alterations remains unknown. The aim of this study is to identify potential tumor rejection antigens for the development of antigen-directed cellular therapies for medulloblastoma.We developed a cancer immunogenomics pipeline and performed a comprehensive analysis of medulloblastoma subgroup-specific transcription profiles (n = 170, 18 WNT, 46 SHH, 41 Group 3, and 65 Group 4 patient tumors) available through International Cancer Genome Consortium (ICGC) and European Genome-Phenome Archive (EGA). We performed in silico antigen prediction across a broad array of antigen classes including neoantigens, tumor-associated antigens (TAAs), and fusion proteins. Furthermore, we evaluated the antigen processing and presentation pathway in tumor cells and the immune infiltrating cell landscape using the latest computational deconvolution methods.Medulloblastoma patients were found to express multiple private and shared immunogenic antigens. The proportion of predicted TAAs was higher than neoantigens and gene fusions for all molecular subgroups, except for sonic hedgehog (SHH), which had a higher neoantigen burden. Importantly, cancer-testis antigens, as well as previously unappreciated neurodevelopmental antigens, were found to be expressed by most patients across all medulloblastoma subgroups. Despite being immunologically cold, medulloblastoma subgroups were found to have distinct immune cell gene signatures.Using a custom antigen prediction pipeline, we identified potential tumor rejection antigens with important implications for the development of immunotherapy for medulloblastoma.© 2024. The Author(s).