The Inflammatory Chemokine CCL5 and Cancer Progression

Abstract

Until recently, inflammatory chemokines were viewed mainly as indispensable “gate keepers” of immunity and inflammation. However, updated research indicates that cancer cells subvert the normal chemokine system and these molecules and their receptors become important constituents of the tumor microenvironment with very different ways to exert tumor-promoting roles. The CCR5 and the CCL5 ligand have been detected in some hematological malignancies, lymphomas, and a great number of solid tumors, but extensive studies on the role of the CCL5/CCR axis were performed only in a limited number of cancers. This review summarizes updated information on the role of CCL5 and its receptor CCR5 in cancer cell proliferation, metastasis, and the formation of an immunosuppressive microenvironment and highlights the development of newer therapeutic strategies aimed to inhibit the binding of CCL5 to CCR5, to inhibit CCL5 secretion, or to inhibit the interactions among tumor cells and the microenvironment leading to CCL5 secretion.

Smoker and non-smoker lung adenocarcinoma is characterized by distinct tumor immune microenvironments

“…Previous studies also demonstrate that the CCL5-CCR5 axis plays an active role in tumor development, acts as a growth factor, stimulates angiogenesis, and participates in immune evasion mechanisms. 32 Furthermore, the CXCL11-CX3CR1 axis performed differently between smoking and nonsmoking status in our analysis, which related to angiogenesis and metastasis of tumors in previous experiments. 33 Considering all the evidence above, smoking has the potential to affect the expression of certain chemokines, thereby leading to activation of CD4 + memory T cells and promoting the development and progression of tumor.…”

The Interaction of Heparin Tetrasaccharides with Chemokine CCL5 Is Modulated by Sulfation Pattern and pH

“…Both CCL5 and CCR1, a major receptor on circulating monocytes, have been proposed as therapeutic targets for cancer-related inflammation (26,27) as well as for infectious diseases (28). Residues Arg-47 and Arg-17 of CCL5 have been shown to play a crucial role in the CCL5-CCR1 binding event (29,30), and the N terminus of CCL5 is known to be crucial for CCR1 signaling (30,31).…”

CCL5/RANTES is important for inducing osteogenesis of human mesenchymal stem cells and is regulated by dexamethasone

“…CCL5 was reported to play important roles in chemo-attraction (3), recruitment of leukocytes to the sites of injury and inflammation, and carcinogenesis (4)(5). In CCL5 deficient mice, the effect of loss of CCL5 is dependent upon different age.…”