Laboratório de Biomedicina do Cérebro, Instituto Estadual do Cérebro Paulo Niemeyer (IECPN), Rio de Janeiro, Brazil.
Laboratório de Biomedicina do Cérebro, Instituto Estadual do Cérebro Paulo Niemeyer (IECPN), Rio de Janeiro, Brazil; Laboratório de Avaliação e Síntese de Substâncias Bioativas (LASSBio®), Instituto Nacional de Ciência e Tecnologia de Fármacos e Medicamentos (INCT-INOFAR), Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
Int Immunopharmacol. 2023 Oct;123:110729. doi: 10.1016/j.intimp.2023.110729. Epub 2023 Aug 1.
Glioblastoma is the most common and lethal primary brain tumor in adults. Despite the available cancer treatments, the recurrence of the tumor is high, and the survival rate is low. New approaches to antitumor therapies are needed. Eosinophils are prominent in allergic diseases and accumulate in several human brain tumors. Recently, the antitumor role of eosinophils has been targeted as eosinophils release several cytotoxic factors that induce cell impairment and death.
Here we aim to evaluate the interaction of the eosinophil and glioblastoma cells, the mechanism involved in the potential killing of the glioblastoma cells by the eosinophils, and how allergy/asthma could confer a better glioblastoma prognosis.
Eosinophils and serum from asthmatic and non-asthmatic donors were cultivated with different glioblastoma cell lines.
Glioblastoma cells recruit eosinophils via GM-CSF signaling, activating and increasing eosinophil survivability and function on a GM-CSF-dependent manner. Eosinophils reduce glioblastoma cells metabolism, proliferation, and migration, via Fas/FasL. Cysteinyl-leukotrienes are accounted for the asthmatic serum enhancement of the glioblastoma cell migration and proliferation. Cysteinyl-leukotrienes enhance glioblastoma cell proliferation and migration, albeit activate eosinophils that suppress glioblastoma cells.
Eosinophils have the potential to be key cells on glioblastoma therapeutics, as allergy and eosinophilia are correlated with a better glioblastoma prognosis. Eosinophils are elicited and attach to glioblastoma cells, where, by its cytotoxic function, via Fas/FasL, hind glioblastoma cell metabolism, proliferation, migration, and induce cell death.
胶质母细胞瘤是成人中最常见和最致命的原发性脑肿瘤。尽管有可用的癌症治疗方法，但肿瘤的复发率很高，生存率很低。需要新的抗肿瘤治疗方法。嗜酸性粒细胞在过敏疾病中很突出，并在几种人类脑肿瘤中积聚。最近，嗜酸性粒细胞的抗肿瘤作用已成为研究目标，因为嗜酸性粒细胞释放几种细胞毒性因子，诱导细胞损伤和死亡。
本研究旨在评估嗜酸性粒细胞与胶质母细胞瘤细胞的相互作用、嗜酸性粒细胞潜在杀伤胶质母细胞瘤细胞的机制，以及过敏/哮喘如何为更好的胶质母细胞瘤预后提供条件。
用不同的胶质母细胞瘤细胞系培养嗜酸性粒细胞和哮喘及非哮喘供体的血清。
胶质母细胞瘤细胞通过 GM-CSF 信号招募嗜酸性粒细胞，通过 GM-CSF 依赖性方式激活和增加嗜酸性粒细胞的存活和功能。嗜酸性粒细胞通过 Fas/FasL 减少胶质母细胞瘤细胞的代谢、增殖和迁移。半胱氨酰白三烯是哮喘血清增强胶质母细胞瘤细胞迁移和增殖的原因。半胱氨酰白三烯增强胶质母细胞瘤细胞的增殖和迁移，但激活嗜酸性粒细胞抑制胶质母细胞瘤细胞。
嗜酸性粒细胞有可能成为胶质母细胞瘤治疗的关键细胞，因为过敏和嗜酸性粒细胞增多与更好的胶质母细胞瘤预后相关。嗜酸性粒细胞被募集并附着在胶质母细胞瘤细胞上，通过 Fas/FasL 发挥其细胞毒性作用，抑制胶质母细胞瘤细胞的代谢、增殖、迁移，并诱导细胞死亡。
