由于突变负荷低，因此潜在的新抗原也较少，急性髓系白血病 (AML) 儿童被认为具有 T 细胞耗尽或“冷”肿瘤微环境，并且可能对 T 细胞定向免疫疗法产生反应的可能性较低。了解儿科 AML 骨髓 (BM) 中 T 细胞和其他微环境群体的组成、表型和空间组织对于为未来的免疫治疗试验提供有关儿科 AML 特有的靶向免疫逃避机制的信息至关重要。在这里，我们对儿科 AML 和非白血病对照的肿瘤免疫微环境进行了多维分析。我们证明，近三分之一的儿科 AML 病例具有免疫浸润的 BM，其特点是 M2 与 M1 样巨噬细胞的比例降低。此外，我们在 BM 中检测到大型 T 细胞网络的存在，无论有或没有共定位 B 细胞，并使用空间转录组学剖析了富含 T 和 B 细胞聚集体的细胞组成。这些分析表明，这些聚集体是 CD8 T 细胞、记忆 B 细胞、浆细胞和/或浆母细胞以及 M1 样巨噬细胞的热点。总的来说，我们的研究提供了儿科 AML 中 BM 免疫微环境的多维特征，并为进一步研究这种破坏性疾病的免疫调节机制指明了起点。© 2024。作者。

Because of the low mutational burden and consequently, fewer potential neoantigens, children with acute myeloid leukemia (AML) are thought to have a T cell-depleted or 'cold' tumor microenvironment and may have a low likelihood of response to T cell-directed immunotherapies. Understanding the composition, phenotype, and spatial organization of T cells and other microenvironmental populations in the pediatric AML bone marrow (BM) is essential for informing future immunotherapeutic trials about targetable immune-evasion mechanisms specific to pediatric AML. Here, we conducted a multidimensional analysis of the tumor immune microenvironment in pediatric AML and non-leukemic controls. We demonstrated that nearly one-third of pediatric AML cases has an immune-infiltrated BM, which is characterized by a decreased ratio of M2- to M1-like macrophages. Furthermore, we detected the presence of large T cell networks, both with and without colocalizing B cells, in the BM and dissected the cellular composition of T- and B cell-rich aggregates using spatial transcriptomics. These analyses revealed that these aggregates are hotspots of CD8+ T cells, memory B cells, plasma cells and/or plasmablasts, and M1-like macrophages. Collectively, our study provides a multidimensional characterization of the BM immune microenvironment in pediatric AML and indicates starting points for further investigations into immunomodulatory mechanisms in this devastating disease.© 2024. The Author(s).