Although interleukin-10 (IL-10) is commonly regarded as an anti-inflammatory, immunosuppressive cytokine that favors tumor escape from immune surveillance, a wealth of evidence is accumulating that IL-10 also possesses some immunostimulating properties. In fact, IL-10 has the pleiotropic ability of influencing positively and negatively the function of innate and adaptive immunity in different experimental models, which makes it questionable to merely categorize this cytokine as a target of anti-immune escape therapeutic strategies or rather, as an immunological adjuvant in the fight against cancer. Here, we review available data about the immunostimulating anticancer properties of IL-10, and in particular, we focus on the hypothesis that in contrast to what occurs in secondary lymphoid organs, IL-10 overexpression within the tumor microenvironment may catalyze cancer immune rejection.
Nitric oxide (NO) is a pleiotropic molecule critical to a number of physiological and pathological processes. The last decade has witnessed major advances in dissecting NO biology and its role in cancer pathogenesis. However, the complexity of the interactions between different levels of NO and several aspects of tumor development/progression has led to apparently conflicting findings. Furthermore, both anti-NO and NO-based anticancer strategies appear effective in several preclinical models. This paradoxical dichotomy is leaving investigators with a double challenge: to determine the net impact of NO on cancer behavior and to define the therapeutic role of NO-centered anticancer strategies. Only a comprehensive and dynamic view of the cascade of molecular and cellular events underlying tumor biology and affected by NO will allow investigators to exploit the potential antitumor properties of drugs interfering with NO metabolism. Available data suggest that NO should be considered neither a universal target nor a magic bullet, but rather a signal transducer to be modulated according to the molecular makeup of each individual cancer and the interplay with conventional antineoplastic agents.
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