Immunomodulation: the role of hematopoietic cytokines

Hematopoietic cytokines have been used primarily as supportive care for patients undergoing cytotoxic chemotherapy or hematopoietic progenitor mobilization. Although the commonly used agents, granulocyte colony-stimulating factor and granulocytemacrophage colony-stimulating factor (GM-CSF), have been used interchangeably, it is clear that they have different effects on immune function and immune priming. GM-CSF has been used for some time as a vaccine adjuvant agent because of its activity on monocytes and dendritic cells. In order to capitalize on the immune activation effects of GM-CSF, numerous groups have transduced the GM-CSF gene into tumor cells in an effort to recruit local inflammatory cells and cytokines to the site of vaccination. Additionally, GM-CSF alone has been demonstrated to have activity for patients with high-risk melanoma and hormone-refractory prostate cancer. This article discusses some of the immune enhancing and suppressive activities of the hematopoietic cytokines, with particular focus on the immunomodulatory effects of GM-CSF, both in the context of single-agent therapy for solid tumors as well as in the context of dendritic cell modulation during therapy for hematopoietic malignancies.