Abstract
ABSTRACT Introduction Chemokines and their cognate receptors play a major role in modulating inflammatory responses. Depending on their ligand binding, chemokine receptors can stimulate both immune activating and inhibitory signaling pathways. The CC chemokine receptor 5 (CCR5) promotes immune responses by recruiting immune cells to the sites of inflammation/tumor, and is involved in stimulating tumor cell proliferation, invasion and migration through various mechanisms. Moreover, CCR5 also contributes to an immune-suppressive tumor microenvironment by recruiting regulatory T cells and myeloid-derived suppressor cells facilitating tumor development and progression. In summary, cells expressing CCR5 modulate immune response and tumor progression. Expression of CCR5 is increased in various malignancies and associated with poor outcome. Experimental data show promising efficacy signals with CCR5 antagonists in preclinical tumor models. Therefore, CCR5 has been recognized as a potential therapeutic target for cancer. Areas covered In this review, we focus on the role of CCR5 in cancer progression and discuss its impact and potential as a therapeutic target for cancer. Expert opinion Beyond immune-checkpoint inhibitors, potentially synergistic immune-modulatory drugs such as CCR5 antagonists are a promising approach to enlarge our treatment armamentarium against cancer.
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