Molecular profiling of the tumour immune microenvironment (TIME) has enabled the rational choice of immunotherapies in some adult cancers. In contrast, the TIME of paediatric cancers is relatively unexplored. We speculated that a more refined appreciation of the TIME in childhood cancers, rather than a reliance on commonly used biomarkers such as tumour mutation burden (TMB), neoantigen load and PD-L1 expression, is an essential prerequisite for improved immunotherapies in childhood solid cancers. We combined immunohistochemistry (IHC) and molecular profiling to develop an alternative, expression-based signature associated with CD8⁺ T-cell infiltration of the TIME in high-risk paediatric tumours. Using this novel 15-gene immune signature, Immune Paediatric Signature Score (IPASS), we estimate up to 31% of high-risk cancers harbour infiltrating T-cells. Our data provides new insights into the variable immune-suppressive mechanisms dampening responses in paediatric solid cancers. Effective immune-based interventions in high-risk paediatric cancer will require individualised analysis of the TIME.

中文翻译：

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一种新的转录特征识别高危儿科癌症中的 T 细胞浸润

肿瘤免疫微环境 (TIME) 的分子谱分析使一些成人癌症的免疫疗法的合理选择成为可能。相比之下，儿童癌症的 TIME 相对未知。我们推测，对儿童癌症中的 TIME 进行更精细的评估，而不是依赖于常用的生物标志物，如肿瘤突变负荷 (TMB)、新抗原负荷和 PD-L1 表达，是改善儿童实体癌免疫治疗的必要先决条件. 我们将免疫组织化学 (IHC) 和分子分析相结合，开发了另一种与 CD8 ^{+相关的基于表达的特征}高危儿科肿瘤中 TIME 的 T 细胞浸润。使用这种新颖的 15 基因免疫特征，免疫儿科特征评分 (IPASS)，我们估计高达 31% 的高危癌症含有浸润性 T 细胞。我们的数据为抑制小儿实体癌反应的可变免疫抑制机制提供了新的见解。对高危儿科癌症进行有效的基于免疫的干预将需要对 TIME 进行个体化分析。