Theron Annette J, Steel Helen C, Rapoport Bernardo L, Anderson Ronald
Department of Immunology, Faculty of Health Sciences, University of Pretoria, Pretoria 0001, South Africa.
The Medical Oncology Centre of Rosebank, Johannesburg 2196, South Africa.
Pharmaceuticals (Basel). 2020 Nov 20;13(11):406. doi: 10.3390/ph13110406.
Tumor cells are particularly adept at exploiting the immunosuppressive potential of neutrophils as a strategy to achieve uncontrolled proliferation and spread. Recruitment of neutrophils, particularly those of an immature phenotype, known as granulocytic myeloid-derived suppressor cells, is achieved via the production of tumor-derived granulocyte colony-stimulating factor (G-CSF) and neutrophil-selective chemokines. This is not the only mechanism by which G-CSF contributes to tumor-mediated immunosuppression. In this context, the G-CSF receptor is expressed on various cells of the adaptive and innate immune systems and is associated with induction of T cell polarization towards the Th2 and regulatory T cell (Treg) phenotypes. In contrast to the potentially adverse effects of sustained, endogenous production of G-CSF by tumor cells, stringently controlled prophylactic administration of recombinant (r) G-CSF is now a widely practiced strategy in medical oncology to prevent, and in some cases treat, chemotherapy-induced severe neutropenia. Following an overview of the synthesis, structure and function of G-CSF and its receptor, the remainder of this review is focused on: (i) effects of G-CSF on the cells of the adaptive and innate immune systems; (ii) mechanisms by which this cytokine promotes tumor progression and invasion; and (iii) current clinical applications and potential risks of the use of rG-CSF in medical oncology.
肿瘤细胞尤其善于利用中性粒细胞的免疫抑制潜能，作为实现不受控制的增殖和扩散的一种策略。中性粒细胞的募集，特别是那些具有未成熟表型的中性粒细胞，即粒细胞髓系来源的抑制细胞，是通过肿瘤衍生的粒细胞集落刺激因子（G-CSF）和中性粒细胞选择性趋化因子的产生来实现的。这并不是G-CSF导致肿瘤介导的免疫抑制的唯一机制。在这种情况下，G-CSF受体在适应性和先天性免疫系统的各种细胞上表达，并与诱导T细胞向Th2和调节性T细胞（Treg）表型极化有关。与肿瘤细胞持续内源性产生G-CSF的潜在不利影响相反，严格控制的重组（r）G-CSF预防性给药现在是医学肿瘤学中广泛采用的一种策略，用于预防并在某些情况下治疗化疗引起的严重中性粒细胞减少症。在概述G-CSF及其受体的合成、结构和功能之后, 本综述的其余部分重点关注：（i）G-CSF对适应性和先天性免疫系统细胞的影响；（ii）这种细胞因子促进肿瘤进展和侵袭的机制；（iii）rG-CSF在医学肿瘤学中的当前临床应用和潜在风险。
