Hambardzumyan Dolores, Gutmann David H, Kettenmann Helmut
Department of Neurosciences, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA.
Department of Neurology, Washington University School of Medicine, St. Louis, Missouri, USA.
Nat Neurosci. 2016 Jan;19(1):20-7. doi: 10.1038/nn.4185.
There is a growing recognition that gliomas are complex tumors composed of neoplastic and non-neoplastic cells, which each individually contribute to cancer formation, progression and response to treatment. The majority of the non-neoplastic cells are tumor-associated macrophages (TAMs), either of peripheral origin or representing brain-intrinsic microglia, that create a supportive stroma for neoplastic cell expansion and invasion. TAMs are recruited to the glioma environment, have immune functions, and can release a wide array of growth factors and cytokines in response to those factors produced by cancer cells. In this manner, TAMs facilitate tumor proliferation, survival and migration. Through such iterative interactions, a unique tumor ecosystem is established, which offers new opportunities for therapeutic targeting.
人们越来越认识到,胶质瘤是由肿瘤细胞和非肿瘤细胞组成的复杂肿瘤,这些细胞各自对癌症的形成、进展和治疗反应都有贡献。大多数非肿瘤细胞是肿瘤相关巨噬细胞(TAM),它们要么起源于外周,要么代表脑内固有小胶质细胞,为肿瘤细胞的扩增和侵袭创造了支持性基质。TAM被招募到胶质瘤环境中,具有免疫功能,并能响应癌细胞产生的那些因子而释放多种生长因子和细胞因子。通过这种方式,TAM促进肿瘤增殖、存活和迁移。通过这种反复的相互作用,建立了一个独特的肿瘤生态系统,这为治疗靶点提供了新的机会。