The Potential for Monocyte-Mediated Immunotherapy During Infection and Malignancy - Part II: In Vivo Activation by Exogenous Cytokines and Clinical Applications

Abstract

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-γ 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-γ 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.Monocytes and their communication with other cells of the immune system play a key role in the regulation of host immunity. Selective modulation of monocyte function by the exogenous therapeutic use of GM-CSF or other cytokines, may improve current treatment of severe infections in immunosuppressed patients. Moreover, monocyte-directed immunotherapy may have applications in those patients undergoing cancer chemotherapy, especially in the context of MRD. The availability of recombinant cytokines has led to renewed optimism in the immunotherapeutic treatment of a whole spectrum of diseases. This is complemented with a resurgence of clinical programs involving monocyte/macrophage activation. Refinements in these protocols and a better understanding of the biological processes involved in the cellular and molecular regulation of host immunity may ultimately produce genuine and sustained benefits.