Systems-level immunomonitoring in children with solid tumors

Cancer is the leading cause of death from disease in children. Survival depends on surgery, cytostatic drugs, radiation, but also systemic immune responses. Factors influencing these immune responses in children of different ages and tumor types are unknown. Novel immunotherapies can enhance anti-tumor immune responses, but few children have benefited, and markers of effective responses are lacking. Here, we present a systems-level analysis of immune responses in 191 children within a population-based cohort with diverse tumors and reveal that age and tumor type shape immune responses differently. Systemic inflammation and cytotoxic T cell responses correlate with tumor mutation rates and immune cell infiltration. Clonally expanded T cell responses are rarely detected in blood or tumors at diagnosis but sometimes elicited during treatment. Expanded T cells are similarly regulated in children and adults with more immunogenic cancers. This research aims to facilitate the development of precision immunotherapies for children with cancer.

This repertoire provides processed raw data of single cell RNA sequencing of paediatric cancer patients as well as the adult data processed from public data sets. More details and scripts to reproduce each figure can be found in https://github.com/Brodinlab/ISAC1

癌症是导致儿童死亡的首要疾病原因。生存与否取决于手术、细胞毒性药物、放射治疗，以及全身性免疫反应。然而，影响不同年龄段和肿瘤类型儿童免疫反应的因素尚不明确。新型免疫治疗能够增强抗肿瘤免疫反应，但受益的儿童寥寥无几，且有效的反应标志物亦未找到。本研究从系统层面分析了191名具有多样化肿瘤的基于人群队列的儿童免疫反应，揭示年龄和肿瘤类型以不同方式塑造免疫反应。系统性炎症和细胞毒性T细胞反应与肿瘤突变率及免疫细胞浸润程度相关。克隆性扩大的T细胞反应在诊断时血液或肿瘤中很少被发现，但在治疗过程中有时会被激发。与具有更强免疫原性的癌症的儿童和成人相比，扩大的T细胞在儿童和成人中受到相似的调控。本研究旨在促进为儿童癌症患者开发精准免疫治疗。本数据集提供了儿童癌症患者以及从公共数据集中处理后的成人数据的单细胞RNA测序的原始数据处理数据。更多细节和重现每个图表的脚本可在https://github.com/Brodinlab/ISAC1找到。