Nitric Oxide, Immunity and Cancer: From Pathogenesis to Therapy

Abstract

Defining the specific role of nitric oxide (NO) in the regulation of the immune response against cancer is not a simple task. Despite of being extensively studied, NO, reactive nitrogen species (RNS) and reactive oxygen species (ROS) still maintain their reputation of "double-edge-swords". However, by examining key issues related to their sources, concentrations and chemical nature and, their locations and neighboring molecules that potentially will be reacting with them, we will have a more precise interpretation of the functional aspects of NO and related RNS in the context of the immune response to tumor cells and pathogenesis of cancer. Variations in the local cellular concentration of the same reactive intermediates induce different outcomes of the immune response. NO and related reactive species trigger defined signal transduction pathways in cancer, and immune-related cells in a concentration-dependent manner. NO bioavailability and NO-dependent responses are strictly functions of the reactivity of ROS with NO-forming RNS. In this chapter, we will examine the basic biology of NO and related species in the context of the immune response to cancer in both their potential role in the pathogenesis of malignancies and also in the control and modulation of the immune response against tumor cells. We will discuss the potential use of NO and related species in the induction of specific anti-cancer activity by the immune system and the modulation of resistance or tolerogenic factors derived from the protective mechanism acquired by the tumor cells in order to evade the anti-tumor immune response.