Pediatric Hematology-Oncology, Blood and Marrow Transplantation, Children's Hospital Los Angeles Saban Research Institute, University of Southern California Keck School of Medicine, 4650 Sunset Blvd, Los Angeles, CA 90027, USA.
Pediatric Hematology-Oncology, City of Hope National Medical Center, 1500 E. Duarte road, Duarte, CA 91010, USA.
Pharmacol Ther. 2019 Dec;204:107403. doi: 10.1016/j.pharmthera.2019.107403. Epub 2019 Aug 27.
Neutrophils form an essential part of innate immunity against infection. Cancer chemotherapy-induced neutropenia (CCIN) is a condition in which the number of neutrophils in a patient's bloodstream is decreased, leading to increased susceptibility to infection. Granulocyte colony-stimulating factor (GCSF) has been the only approved treatment for CCIN over two decades. To date, CCIN-related infection and mortality remain a significant concern, as neutrophils generated in response to administered GCSF are functionally immature and cannot effectively fight infection. This review summarizes the molecular regulatory mechanisms of neutrophil granulocytic differentiation and innate immunity development, dissects the biology of GCSF in myeloid expansion, highlights the shortcomings of GCSF in CCIN treatment, updates the recent advance of a selective retinoid agonist that promotes neutrophil granulocytic differentiation, and evaluates the benefits of developing GCSF biosimilars to increase access to GCSF biologics versus seeking a new mode to fundamentally advance GCSF therapy for treatment of CCIN.
中性粒细胞是抵御感染的先天免疫的重要组成部分。癌症化疗诱导的中性粒细胞减少症（CCIN）是一种患者血液中中性粒细胞数量减少的情况，导致易感染。粒细胞集落刺激因子（GCSF）在过去的二十年中一直是 CCIN 的唯一批准治疗方法。迄今为止，与 CCIN 相关的感染和死亡率仍然是一个令人关注的问题，因为对给予的 GCSF 产生的中性粒细胞在功能上不成熟，无法有效抵抗感染。这篇综述总结了中性粒细胞粒细胞分化和先天免疫发育的分子调节机制，剖析了 GCSF 在髓系扩增中的生物学作用，强调了 GCSF 在 CCIN 治疗中的缺点，更新了最近促进中性粒细胞粒细胞分化的选择性维甲酸激动剂的进展，并评估了开发 GCSF 生物类似物的好处，以增加 GCSF 生物制剂的可及性，而不是寻求新的模式从根本上推进 GCSF 治疗 CCIN。
