Granulocyte-macrophage-colony-stimulating factor and other cytokines: as adjuncts to cancer immunotherapy, stem cell transplantation, and vaccines.

A new role for myeloid-acting cytokines in regulating immune responses has been proposed based upon their activity on dendritic cell (DC) maturation and activation. Subsets of DCs may augment or inhibit cellular immune responses. Enhanced DC1 activity has been associated with enhanced cytotoxic immune responses. Granulocyte-macrophage-colony-stimulating factor (GM-CSF) and granulocyte-colony- stimulating factor (G-CSF) differ by their effects on enhancing the numbers or activity of DC1 or DC2 subsets of DCs, respectively. The increase in DC1 content and activity following local and systemic GM-CSF administration support a role for GM-CSF as an immune stimulant and vaccine adjuvant in cancer patients. The clinical activity of GM-CSF in anti-tumor immune responses has been documented in its use in tumor cell and DC vaccines, but a significant anti-tumor effect of parenterally administered GM-CSF in a randomized clinical study has yet to be consistently demonstrated. The successful use of myeloid acting cytokines to enhance anti-tumor responses will likely require targeting these drugs or activating DCs directly into the tumor microenvironment.