Kast Richard E, Hill Quentin A, Wion Didier, Mellstedt Håkan, Focosi Daniele, Karpel-Massler Georg, Heiland Tim, Halatsch Marc-Eric
1 IIAIGC Study Center, Burlington, VT, USA.
2 Department of Haematology, St James's University Hospital, Leeds Teaching Hospitals, Leeds, UK.
Tumour Biol. 2017 May;39(5):1010428317699797. doi: 10.1177/1010428317699797.
Increased ratio of circulating neutrophils to lymphocytes is a common finding in glioblastoma and other cancers. Data reviewed establish that any damage to brain tissue tends to cause an increase in G-CSF and/or GM-CSF (G(M)-CSF) synthesized by the brain. Glioblastoma cells themselves also synthesize G(M)-CSF. G(M)-CSF synthesized by brain due to damage by a growing tumor and by the tumor itself stimulates bone marrow to shift hematopoiesis toward granulocytic lineages away from lymphocytic lineages. This shift is immunosuppressive and generates the relative lymphopenia characteristic of glioblastoma. Any trauma to brain-be it blunt, sharp, ischemic, infectious, cytotoxic, tumor encroachment, or radiation-increases brain synthesis of G(M)-CSF. G(M)-CSF are growth and motility enhancing factors for glioblastomas. High levels of G(M)-CSF contribute to the characteristic neutrophilia and lymphopenia of glioblastoma. Hematopoietic bone marrow becomes entrained with, directed by, and contributes to glioblastoma pathology. The antibiotic dapsone, the lipid-lowering agent fenofibrate, and the antiviral drug ribavirin are Food and Drug Administration- and European Medicines Agency-approved medicines that have potential to lower synthesis or effects of G(M)-CSF and thus deprive a glioblastoma of some of the growth promoting contributions of bone marrow and G(M)-CSF.
循环中性粒细胞与淋巴细胞的比例增加是胶质母细胞瘤和其他癌症中的常见现象。所审查的数据表明，对脑组织的任何损伤往往会导致大脑合成的粒细胞集落刺激因子（G-CSF）和/或粒细胞-巨噬细胞集落刺激因子（GM-CSF，G(M)-CSF）增加。胶质母细胞瘤细胞自身也会合成G(M)-CSF。由于不断生长的肿瘤造成的损伤以及肿瘤自身的损伤，大脑合成的G(M)-CSF会刺激骨髓将造血作用从淋巴细胞系转向粒细胞系。这种转变具有免疫抑制作用，并产生了胶质母细胞瘤特有的相对淋巴细胞减少。对大脑的任何创伤——无论是钝性、锐性、缺血性、感染性、细胞毒性、肿瘤侵犯还是放射性创伤——都会增加大脑对G(M)-CSF的合成。G(M)-CSF是胶质母细胞瘤的生长和运动增强因子。高水平的G(M)-CSF导致了胶质母细胞瘤特有的中性粒细胞增多和淋巴细胞减少。造血骨髓被卷入胶质母细胞瘤的病理过程中，受其引导并对其产生影响。抗生素氨苯砜、降脂药物非诺贝特和抗病毒药物利巴韦林是美国食品药品监督管理局和欧洲药品管理局批准的药物，它们有可能降低G(M)-CSF的合成或作用，从而剥夺胶质母细胞瘤从骨髓和G(M)-CSF获得的一些促进生长的作用。
