Experimental and clinical studies indicate that cells of the innate and adaptive immune system have both anti- and pro-tumor activities. This dual role of the immune system has led to a conceptual shift in the role of the immune system’s regulation of cancer, in which immune-tumor cell interactions are understood as a dynamic process that comprises at least five phases: immunosurveillance, immunoselection, immunoescape, oncotraining, and oncopromotion. The tumor microenvironment shifts immune cells to perform functions more in tune with the tumor needs (oncotraining); these functions are related to chronic inflammation and tissue remodeling activities. Among them are increased proliferation and survival, increased angiogenesis and vessel permeability, protease secretion, acquisition of migratory mesenchymal characteristics, and self-renewal properties that altogether promote tumor growth and metastasis (oncopromotion). Important populations in all these pro-tumor processes are M2 macrophages, N2 neutrophils, regulatory T cells, and myeloid derived suppressor cells; the main effectors molecules are CSF-1, IL-6, metalloproteases, VEGF, PGE-2, TGF-β, and IL-10. Cancer prognosis correlates with densities and concentrations of protumoral populations and molecules, providing ideal targets for the intelligent design of directed preventive or anticancer therapies. 1. Introduction Somatic cells are in constant risk of cancer transformation and organisms are endowed with surveillance mechanisms carried out by the immune system to control the generation of cancer cells. These mechanisms are (i) controlling infection by oncogenic pathogens, (ii) resolving local inflammation to prevent the establishment of a tumorigenic chronic inflammatory microenvironment, and (iii) eliminating potentially transformed cells. The AIDS pandemic and laboratory recombinant technologies have provided plenty of support to the Burnet and Thomas hypothesis of immunosurveillance (Figure 1) [1, 2]. However, increasing understanding of the relationship between the immune system and cancer points out that there is more than one side to this tale, with more recent evidence supporting a role for the immune system in promoting oncogenesis and tumor growth [3, 4]. This duality displayed by the immune system has led to the concept of an “immunological shift” in cancer, in which immune and transformed cells interact in a dynamic process comprising at least five phases: immunosurveillance, immunoselection, immunoescape, oncotraining, and oncopromotion. The first phase represents a functional immune
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