Abstract:
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 e ects
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) e ects 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.
