Department of Pediatrics, Neuro-Oncology Division and Aflac Cancer and Blood Disorders Center of Children's Healthcare of Atlanta, Emory University, Atlanta, 30322, GA, United States.
Winship Cancer Institute, Emory University, Atlanta, 30322, GA, USA.
Nat Commun. 2019 Jun 3;10(1):2410. doi: 10.1038/s41467-019-10458-9.
Medulloblastoma, which is the most common malignant paediatric brain tumour, has a 70% survival rate, but standard treatments often lead to devastating life-long side effects and recurrence is fatal. One of the emerging strategies in the search for treatments is to determine the roles of tumour microenvironment cells in the growth and maintenance of tumours. The most attractive target is tumour-associated macrophages (TAMs), which are abundantly present in the Sonic Hedgehog (SHH) subgroup of medulloblastoma. Here, we report an unexpected beneficial role of TAMs in SHH medulloblastoma. In human patients, decreased macrophage number is correlated with significantly poorer outcome. We confirm macrophage anti-tumoural behaviour in both ex vivo and in vivo murine models of SHH medulloblastoma. Taken together, our findings suggest that macrophages play a positive role by impairing tumour growth in medulloblastoma, in contrast to the pro-tumoural role played by TAMs in glioblastoma, another common brain tumour.
髓母细胞瘤是最常见的儿童脑部恶性肿瘤，其存活率为 70%，但标准治疗往往会导致毁灭性的终身副作用，且肿瘤复发则是致命的。在寻找治疗方法的新兴策略中，其中之一是确定肿瘤微环境细胞在肿瘤生长和维持中的作用。最有吸引力的靶标是肿瘤相关巨噬细胞（TAMs），它们在 Sonic Hedgehog（SHH）髓母细胞瘤亚群中大量存在。在这里，我们报告了 TAMs 在 SHH 髓母细胞瘤中的一个意外的有益作用。在人类患者中，巨噬细胞数量的减少与预后显著恶化相关。我们在 SHH 髓母细胞瘤的离体和体内小鼠模型中证实了巨噬细胞的抗肿瘤行为。总之，我们的发现表明，巨噬细胞通过削弱髓母细胞瘤中的肿瘤生长发挥积极作用，这与 TAMs 在另一种常见的脑部肿瘤——胶质母细胞瘤中发挥的促肿瘤作用形成对比。
