Department of Neurological Surgery, University of Pittsburgh, Pittsburgh, PA, USA.
School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
Expert Rev Clin Immunol. 2024 Nov;20(11):1411-1420. doi: 10.1080/1744666X.2024.2390023. Epub 2024 Aug 18.
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.
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.
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.
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.
尽管进行了手术切除、放化疗和靶向治疗，脑肿瘤仍然是儿童癌症相关死亡的主要原因。免疫疗法已经显示出一些希望，并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关键步骤是发现可以有效转化为治疗干预的靶点。
在这项研究中，我们的团队对儿科脑肿瘤类型进行了转录组分析，以确定免疫疗法的潜在靶点。此外，我们评估了可能影响患者对免疫疗法反应的因素，包括抗原处理和呈递所必需基因的表达、抑制性配体和受体、干扰素特征以及整体预测的 T 细胞浸润。
我们观察到肿瘤类型之间存在明显的表达模式。其中一些肿瘤类型中抗原基因和抗原处理机制表达上调，而其他肿瘤类型中抑制性检查点受体表达上调，这些受体已知与对检查点抑制剂免疫疗法的反应相关。
这些发现表明，小儿脑肿瘤具有特定免疫疗法的明显潜力。我们相信，我们的发现可以指导研究人员评估小儿脑肿瘤中适当的免疫治疗类别和靶点。
