Transcriptomic observations of intra and extracellular immunotherapy targets for pediatric brain tumors.

IF 3.9 3区 医学 Q2 IMMUNOLOGY
Stephen C Frederico, Itay Raphael, Michal Nisnboym, Sakibul Huq, Brent T Schlegel, Chaim T Sneiderman, Sydney A Jackson, Anya Jain, Michael R Olin, Brian R Rood, Ian F Pollack, Eugene I Hwang, Dhivyaa Rajasundaram, Gary Kohanbash
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Abstract

Objectives: Despite surgical resection, chemoradiation, and targeted therapy, brain tumors remain a leading cause of cancer-related death in children. Immunotherapy has shown some promise and is actively being investigated for treating childhood brain tumors. However, a critical step in advancing immunotherapy for these patients is to uncover targets that can be effectively translated into therapeutic interventions.

Methods: In this study, our team performed a transcriptomic analysis across pediatric brain tumor types to identify potential targets for immunotherapy. Additionally, we assessed components that may impact patient response to immunotherapy, including the expression of genes essential for antigen processing and presentation, inhibitory ligands and receptors, interferon signature, and overall predicted T cell infiltration.

Results: We observed distinct expression patterns across tumor types. These included elevated expression of antigen genes and antigen processing machinery in some tumor types while other tumors had elevated inhibitory checkpoint receptors, known to be associated with response to checkpoint inhibitor immunotherapy.

Conclusion: These findings suggest that pediatric brain tumors exhibit distinct potential for specific immunotherapies. We believe our findings can guide investigators in their assessment of appropriate immunotherapy classes and targets in pediatric brain tumors.

小儿脑肿瘤细胞内和细胞外免疫疗法靶点的转录组观察。
目标:尽管采取了手术切除、化学放疗和靶向治疗等方法,脑肿瘤仍然是导致儿童癌症相关死亡的主要原因。免疫疗法已显示出一定的前景,目前正在积极研究用于治疗儿童脑肿瘤。然而,为这些患者推进免疫疗法的一个关键步骤是发现可有效转化为治疗干预措施的靶点:在这项研究中,我们的团队对各种类型的儿童脑肿瘤进行了转录组分析,以确定免疫疗法的潜在靶点。此外,我们还评估了可能影响患者对免疫疗法反应的成分,包括抗原处理和递呈、抑制性配体和受体、干扰素特征以及总体预测的T细胞浸润所必需的基因的表达:结果:我们观察到不同肿瘤类型有不同的表达模式。结果:我们观察到不同肿瘤类型有不同的表达模式,包括一些肿瘤类型中抗原基因和抗原处理机制的表达升高,而另一些肿瘤中抑制性检查点受体的表达升高,已知这与检查点抑制剂免疫疗法的反应有关:这些发现表明,小儿脑肿瘤对特异性免疫疗法具有独特的潜力。我们相信,我们的研究结果可以指导研究人员评估小儿脑肿瘤的适当免疫疗法类别和靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
7.60
自引率
2.30%
发文量
221
审稿时长
6-12 weeks
期刊介绍: Expert Review of Clinical Immunology (ISSN 1744-666X) provides expert analysis and commentary regarding the performance of new therapeutic and diagnostic modalities in clinical immunology. Members of the International Editorial Advisory Panel of Expert Review of Clinical Immunology are the forefront of their area of expertise. This panel works with our dedicated editorial team to identify the most important and topical review themes and the corresponding expert(s) most appropriate to provide commentary and analysis. All articles are subject to rigorous peer-review, and the finished reviews provide an essential contribution to decision-making in clinical immunology. Articles focus on the following key areas: • Therapeutic overviews of specific immunologic disorders highlighting optimal therapy and prospects for new medicines • Performance and benefits of newly approved therapeutic agents • New diagnostic approaches • Screening and patient stratification • Pharmacoeconomic studies • New therapeutic indications for existing therapies • Adverse effects, occurrence and reduction • Prospects for medicines in late-stage trials approaching regulatory approval • Novel treatment strategies • Epidemiological studies • Commentary and comparison of treatment guidelines Topics include infection and immunity, inflammation, host defense mechanisms, congenital and acquired immunodeficiencies, anaphylaxis and allergy, systemic immune diseases, organ-specific inflammatory diseases, transplantation immunology, endocrinology and diabetes, cancer immunology, neuroimmunology and hematological diseases.
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