The potential for monocyte-mediated immunotherapy during infection and malignancy - Part II: In vivo activation by exogenous cytokines and clinical applications

The monocyte system exhibits a range of immunological mechanisms that may b e harnessed for therapeutic effect against infection and malignancy. The ad vent of novel therapies aimed at treating infection and malignancy is compl emented by a resurgence of clinical interest in immunotherapeutic programme s to treat diseases by modification or direct augmentation of host immunity . Cytokines such as granulocyte-macrophage colony-stimulating factor (GM-CS F) and IFN-gamma modulate the function of monocytes and have been used to e xperimentally probe the immunotherapeutic potential of monocytes against mi cro-organisms and malignancy. However, monocytes rarely act alone but commu nicate with other leukocytes involved in cell-mediated immunity. In particu lar monocytes cooperate with the T-helper (Th1 and Th2) sub-populations of peripheral lymphocytes. Moreover, sub-populations of monocytes, as identifi ed by the co-expression of membrane-associated CD14 and CD16, have been sho wn to exist. At the preclinical level, this provides a unique opportunity t o explore the effect of immunotherapeutic strategies on the function of mon ocyte sub-populations against infectious or malignant challenge and may all ow immunotherapeutic strategies to be targeted towards specific monocyte su b-populations. Preclinical and clinical studies in human subjects suggest t hat GM-CSF and other cytokines such as IFN-gamma are the most promising bio logical response modifiers for augmenting monocyte-mediated immunity. In th is review, the immunotherapeutic potential of the monocyte system will be d iscussed in the context of combating microbial and malignant disease.