Solid tumors are embedded in a stromal microenvironment consisting of immune cells, such as macrophages and lymphocytes, as well as nonimmune cells, such as endothelial cells and fibroblasts. Chemokines are a type of small secreted chemotactic cytokine and together with their receptors play key roles in the immune defense. Critically, they regulate cancer cellular migration and also contribute to their proliferation and survival. The CCR5 chemokine receptor is involved in leucocytes chemotaxis to sites of inflammation and plays an important role in the macrophages, T cells, and monocytes recruitment. Additionally, CCR5 may have an indirect effect on cancer progression by controlling the antitumor immune response, since it has been demonstrated that its expression could promote tumor growth and contribute to tumor metastasis, in different types of malignant tumors. Furthermore, it was demonstrated that a CCR5 antagonist may inhibit tumor growth, consisting of a possible therapeutic target. In this context, the present review focuses on the establishment of CCR5 within the interface of host immunity, tumor microenvironment, and its potential as a targeting to immunotherapy. 1. Introduction Chemokines are a type of small secreted chemotactic cytokine. Together with their receptors, they play key roles in the immune defense by directing and controlling the migration, activation, differentiation, and survival in the physiology of acute and chronic inflammatory processes as well as in the pathological deregulations by attracting and simulating the various subsets of specific leukocytes [1]. Moreover, chemokines critically regulate cancer cellular migration and also contribute to their proliferation and survival [2]. The identification of a large number of chemokine receptors and their selectivity characterization and expression have provided information on the traffic regulation of leukocytes in health and disease. They are expressed on different types of leukocytes constitutively or induced, depending on cell types [3]. The chemokine system is often thought as showing significant redundancy since one receptor can bind multiple ligands, and conversely, a single ligand can bind several chemokine receptors [4]. However, differential spatio-temporal expression patterns for different chemokines and receptors in our body indicate that they probably have distinct roles in vivo [5]. To date, about 45 chemokines and 20 chemokine receptors have been identified and are grouped into four categories (C, CC, CXC, and CX3C) based on the location of the main cysteine
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