The Impact of Resolution of Inflammation on Tumor Microenvironment: Exploring New Ways to Control Cancer Progression

SIMPLE SUMMARY: The evolution of cancer is strongly influenced by the context in which tumor cells develop and grow, known as the tumor microenvironment (TME). The TME is constituted of a set of cells with different natures, which can produce various factors or interact with cancer cells, thus favoring or inhibiting cancer growth. Specific factors with the ability to shape the TME, in order to create an unfavorable context for tumor cells, are the Specialized Pro-resolving Mediators (SPMs). SPMs are small lipid molecules derived from ω-3 and ω-6 fatty acids, exerting the physiologic role of dampening the inflammatory responses and helping tissues to regain their homeostasis after insults. Here, we present the knowledge relative to the action of SPMs on each component of the TME and its effects on tumor growth and progression. These summarized findings highlight novel potential strategies to manage cancer progression. ABSTRACT: Non-resolving inflammation is an enabling feature of cancer. A novel super-family of lipid mediators termed Specialized Pro-resolving Mediators (SPMs) have a role as bioactive molecules mediating the resolution of inflammation in cancer biology. SPMs are derived from ω-3 and ω-6 polyunsaturated fatty acids through the activity of lipoxygenases. SPMs have been described to directly modulate cancer progression by interfering with the epithelial to mesenchymal transition and invasion of cancer cells. SPMs have also been demonstrated to act on several components of the tumor microenvironment (TME). Consistently with their natural immunomodulatory and anti-inflammatory properties, SPMs are able to reprogram macrophages to favor phagocytosis of cell debris, which are an important source of pro-inflammatory and pro-angiogenic signals; sustain a direct cytotoxic immune response against cancer cells; stimulate neutrophils anti-tumor activities; and inhibit the development of regulatory T and B cells, thus indirectly leading to enhanced anti-tumor immunity. Furthermore, the resolution pathways exert crucial anti-angiogenic functions in lung, liver, and gastrointestinal cancers, and inhibit cancer-associated fibroblast differentiation and functions in hepatocellular carcinoma and pancreatic cancer. The present review will be focused on the potential protective effects of resolution pathways against cancer, exerted by modulating different components of the TME.