德国霍普儿童癌症中心Till Milde小组的研究开发出了儿童低级别胶质瘤中MAPK激活的免疫抑制髓细胞群的空间图。相关论文于2025年9月15日发表在《自然—免疫学》杂志上。

在这里，研究人员以成像细胞术为主题，在单细胞水平上对120例pLGG病例的肿瘤微环境（TME）进行了空间表征，考虑了年龄、分子驱动因素、脑位置和肿瘤亚型。他们的分析确定髓系细胞——包括常驻小胶质细胞和骨髓来源的巨噬细胞——是TME中主要的免疫群体，特别是在视神经通路肿瘤中。

此外，研究小组还发现了一种预测无进展生存期的免疫特征。空间分析发现了特定的细胞相互作用，特别是髓-髓细胞接触和巨噬细胞富集区域，这些区域含有MAPK激活的TIM-3⁺髓细胞，表明TME具有免疫抑制作用。他们的研究提供了对这些pLGGs免疫景观的全面抵抗，并强调了多种骨髓浸润的免疫抑制作用。这些发现还表明，结合TIM-3阻断和MAPK抑制可能是一种有希望的治疗策略，可以同时针对pLGG肿瘤的TME和致癌MAPK激活。

据了解，小儿低级别胶质瘤（pLGGs）是一种在儿童中普遍存在的丝裂原活化蛋白激酶（MAPK）途径激活的脑肿瘤，尽管生存率较高，但其发病率较高。

附：英文原文

Title: A spatial map of MAPK-activated immunosuppressive myeloid populations in pediatric low-grade glioma

Author: Andrade, Augusto Faria, Sigaud, Romain, Puligandla, Evan, Liu, Bridget, Karimi, Elham, Annett, Alva, Rezanejad, Morteza, Jawhar, Wajih, Taylor, Robert, Cao, Yi, Schmid, Simone, Selt, Florian, Herniz Driever, Pablo, Horn, Svea, Sievers, Philipp, Prinz, Marco, Glatzel, Markus, Mawrin, Christian, Hartmann, Christian, Monoranu, Camelia-Maria, Konnikova, Liza, Sahm, Felix, Pfister, Stefan M., Witt, Olaf, Jones, David T. W., Koch, Arend, Kleinman, Claudia L., Capper, David, Walsh, Logan, Jabado, Nada, Milde, Till

Issue&Volume: 2025-09-15

Abstract: Pediatric low-grade gliomas (pLGGs) are mitogen-activated protein kinase (MAPK) pathway-activated brain tumors prevalent in children and are associated with morbidity despite favorable survival. Here using imaging mass cytometry, we spatially characterized at the single-cell level the tumor microenvironment (TME) of 120 pLGG cases, considering age, molecular drivers, brain location and tumor subtype. Our analysis identified myeloid cells—including resident microglia and bone marrow-derived macrophages—as the predominant immune population in the TME, particularly in optic pathway tumors. Additionally, we discovered an immune signature predictive of progression-free survival. Spatial analysis identified specific cellular interactions, notably myeloid–myeloid contacts and macrophage-enriched regions harboring MAPK-activated, TIM-3+ myeloid cells, suggesting an immunosuppressive TME. Our study provides a comprehensive resource on the immune landscape of these pLGGs and underscores the immunosuppressive role of diverse myeloid infiltrates. These findings also indicate that combining TIM-3 blockade with MAPK inhibition might be a promising therapeutic strategy to target both the TME and oncogenic MAPK activation in pLGG tumors.

DOI: 10.1038/s41590-025-02268-7

Source: https://www.nature.com/articles/s41590-025-02268-7