Division of Gastroenterology, Boston Children's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Department of Translational Medical Sciences and Center for Basic and Clinical Immunology Research (CISI), University of Naples Federico II, 80131 Naples, Italy.
Int J Mol Sci. 2019 Feb 15;20(4):834. doi: 10.3390/ijms20040834.
Granulocyte-macrophage colony-stimulating factor (GM-CSF) and inteleukin-3 (IL-3) have long been known as mediators of emergency myelopoiesis, but recent evidence has highlighted their critical role in modulating innate immune effector functions in mice and humans. This new wealth of knowledge has uncovered novel aspects of the pathogenesis of a range of disorders, including infectious, neoplastic, autoimmune, allergic and cardiovascular diseases. Consequently, GM-CSF and IL-3 are now being investigated as therapeutic targets for some of these disorders, and some phase I/II clinical trials are already showing promising results. There is also pre-clinical and clinical evidence that GM-CSF can be an effective immunostimulatory agent when being combined with anti-cytotoxic T lymphocyte-associated protein 4 (anti-CTLA-4) in patients with metastatic melanoma as well as in novel cancer immunotherapy approaches. Finally, GM-CSF and to a lesser extent IL-3 play a critical role in experimental models of trained immunity by acting not only on bone marrow precursors but also directly on mature myeloid cells. Altogether, characterizing GM-CSF and IL-3 as central mediators of innate immune activation is poised to open new therapeutic avenues for several immune-mediated disorders and define their potential in the context of immunotherapies.
粒细胞-巨噬细胞集落刺激因子 (GM-CSF) 和白细胞介素-3 (IL-3) 长期以来一直被认为是应急髓系造血的介质，但最近的证据强调了它们在调节小鼠和人类固有免疫效应功能方面的关键作用。这一新的知识财富揭示了一系列疾病发病机制的新方面，包括感染、肿瘤、自身免疫、过敏和心血管疾病。因此，GM-CSF 和 IL-3 现在正在作为这些疾病的一些治疗靶点进行研究，一些 I/II 期临床试验已经显示出有希望的结果。也有临床前和临床证据表明，GM-CSF 可以与抗细胞毒性 T 淋巴细胞相关蛋白 4 (抗 CTLA-4) 联合使用，在转移性黑色素瘤患者以及新型癌症免疫治疗方法中作为一种有效的免疫刺激剂。最后，GM-CSF 和在较小程度上的 IL-3 通过不仅作用于骨髓前体，而且直接作用于成熟髓样细胞，在训练免疫的实验模型中发挥关键作用。总之，将 GM-CSF 和 IL-3 描述为固有免疫激活的中心介质，有望为几种免疫介导的疾病开辟新的治疗途径，并确定它们在免疫治疗中的潜力。
