基于整合多组学的髓母细胞瘤自然呈递T细胞抗原定位

IF 15.7 1区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES
Julia Velz, Lena K. Freudenmann, Gioele Medici, Marissa Dubbelaar, Malte Mohme, David R. Ghasemi, Jonas Scheid, Daniel J. Kowalewski, Angelica B. Patterson, Anna M. Zeitlberger, Katrin Lamszus, Manfred Westphal, Matthias Eyrich, Martina Messing-Jünger, Andreas Röhrig, Harald Reinhard, Kévin Beccaria, Rogeiro B. Craveiro, Beat M. Frey, Martin Sill, Sven Nahnsen, Marie Gauder, Konstantina Kapolou, Manuela Silginer, Tobias Weiss, Hans-Georg Wirsching, Patrick Roth, Michael Grotzer, Niklaus Krayenbühl, Oliver Bozinov, Luca Regli, Hans-Georg Rammensee, Elisabeth J. Rushing, Felix Sahm, Juliane S. Walz, Michael Weller, Marian C. Neidert
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引用次数: 0

摘要

髓母细胞瘤是儿童最常见的原发性恶性脑肿瘤。尽管整合基因组学最近取得了进展,但高风险髓母细胞瘤儿童的预后仍然是毁灭性的,需要新的肿瘤特异性治疗方法。在这里,我们展示了髓母细胞瘤中自然呈现的T细胞抗原图谱。我们绘制了28种肿瘤的人类白细胞抗原(HLA)呈现的肽酶,并对内部良性数据库进行了比较免疫肽酶分析。髓母细胞瘤是肿瘤相关抗原的丰富来源,自然呈现在HLA I类和II类分子上。值得注意的是,大多数肿瘤相关肽和蛋白是亚群特异性的,而髓母细胞瘤所有亚群(WNT, SHH, Group 3和Group 4)的共同表现是罕见的。顶级的新候选抗原的功能测试证明了肽特异性T细胞反应的诱导,支持它们在T细胞免疫治疗中的潜力。这项研究是对髓母细胞瘤中自然呈现的T细胞抗原的深入定位。免疫肽组学、转录组学和表观遗传学数据的整合导致了大量可操作靶点的识别,这些靶点可以通过促进对髓母细胞瘤儿童免疫治疗方法的知情设计,进一步用于转化为临床环境。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Mapping naturally presented T cell antigens in medulloblastoma based on integrative multi-omics

Mapping naturally presented T cell antigens in medulloblastoma based on integrative multi-omics

Medulloblastoma is the most frequent malignant primary brain tumor in children. Despite recent advances in integrated genomics, the prognosis in children with high-risk medulloblastoma remains devastating, and new tumor-specific therapeutic approaches are needed. Here, we present an atlas of naturally presented T cell antigens in medulloblastoma. We map the human leukocyte antigen (HLA)-presented peptidomes of 28 tumors and perform comparative immunopeptidome profiling against an in-house benign database. Medulloblastoma is shown to be a rich source of tumor-associated antigens, naturally presented on HLA class I and II molecules. Remarkably, most tumor-associated peptides and proteins are subgroup-specific, whereas shared presentation among all subgroups of medulloblastoma (WNT, SHH, Group 3 and Group 4) is rare. Functional testing of top-ranking novel candidate antigens demonstrates the induction of peptide-specific T cell responses, supporting their potential for T cell immunotherapy. This study is an in-depth mapping of naturally presented T cell antigens in medulloblastoma. Integration of immunopeptidomics, transcriptomics, and epigenetic data leads to the identification of a large set of actionable targets that can be further used for the translation into the clinical setting by facilitating the informed design of immunotherapeutic approaches to children with medulloblastoma.

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来源期刊
Nature Communications
Nature Communications Biological Science Disciplines-
CiteScore
24.90
自引率
2.40%
发文量
6928
审稿时长
3.7 months
期刊介绍: Nature Communications, an open-access journal, publishes high-quality research spanning all areas of the natural sciences. Papers featured in the journal showcase significant advances relevant to specialists in each respective field. With a 2-year impact factor of 16.6 (2022) and a median time of 8 days from submission to the first editorial decision, Nature Communications is committed to rapid dissemination of research findings. As a multidisciplinary journal, it welcomes contributions from biological, health, physical, chemical, Earth, social, mathematical, applied, and engineering sciences, aiming to highlight important breakthroughs within each domain.
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