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 be harnessed for therapeutic effect against infection and malignancy. The advent of novel therapies aimed at treating infection and malignancy is complemented by a resurgence of clinical interest in immunotherapeutic programmes to treat diseases by modification or direct augmentation of host immunity. Cytokines such as granulocyte-macrophage colony-stimulating factor (GM-CSF) and IFN-gamma modulate the function of monocytes and have been used to experimentally probe the immunotherapeutic potential of monocytes against micro-organisms and malignancy. However, monocytes rarely act alone but communicate with other leukocytes involved in cell-mediated immunity. In particular monocytes cooperate with the T-helper (Th1 and Th2) sub-populations of peripheral lymphocytes. Moreover, sub-populations of monocytes, as identified by the co-expression of membrane-associated CD14 and CD16, have been shown to exist. At the preclinical level, this provides a unique opportunity to explore the effect of immunotherapeutic strategies on the function of monocyte sub-populations against infectious or malignant challenge and may allow immunotherapeutic strategies to be targeted towards specific monocyte sub-populations. Preclinical and clinical studies in human subjects suggest that GM-CSF and other cytokines such as IFN-gamma are the most promising biological response modifiers for augmenting monocyte-mediated immunity. In this review, the immunotherapeutic potential of the monocyte system will be discussed in the context of combating microbial and malignant disease.