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Inhibition of the CCL5/CCR5 Axis against the Progression of Gastric Cancer

Department of Molecular Oncology, CRO Aviano National Cancer Institute, via F. Gallini 2, I-33081 Aviano, Italy
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2018, 19(5), 1477;
Received: 26 April 2018 / Revised: 11 May 2018 / Accepted: 14 May 2018 / Published: 16 May 2018
(This article belongs to the Special Issue Molecular Features Distinguishing Gastric Cancer Subtypes)
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Despite the progress made in molecular and clinical research, patients with advanced-stage gastric cancer (GC) have a bad prognosis and very low survival rates. Furthermore, it is challenging to find the complex molecular mechanisms that are involved in the development of GC, its progression, and its resistance to therapy. The interactions of chemokines, also known as chemotactic cytokines, with their receptors regulate immune and inflammatory responses. However, updated research demonstrates that cancer cells subvert the normal chemokine role, transforming them into fundamental constituents of the tumor microenvironment (TME) with tumor-promoting effects. C-C chemokine ligand 5 (CCL5) is a chemotactic cytokine, and its expression and secretion are regulated in T cells. C-C chemokine receptor type 5 (CCR5) is expressed in T cells, macrophages, other leukocytes, and certain types of cancer cells. The interaction between CCL5 and CCR5 plays an active role in recruiting leukocytes into target sites. This review summarizes recent information on the role of the CCL5 chemokine and its receptor CCR5 in GC cell proliferation, metastasis formation, and in the building of an immunosuppressive TME. Moreover, it highlights the development of new therapeutic strategies to inhibit the CCL5/CCR5 axis in different ways and their possible clinical relevance in the treatment of GC. View Full-Text
Keywords: CCL5; CCR5; gastric cancer; tumor microenvironment; invasion; CCR5 antagonists CCL5; CCR5; gastric cancer; tumor microenvironment; invasion; CCR5 antagonists

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Aldinucci, D.; Casagrande, N. Inhibition of the CCL5/CCR5 Axis against the Progression of Gastric Cancer. Int. J. Mol. Sci. 2018, 19, 1477.

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