CCR5 is a potential therapeutic target for cancer

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.

KEYWORDS:

• Chemokine
• chemokine receptors
• ccr5
• cancer
• therapeutic target

Article highlights

• Chemokines modulate immune responses by mediating pro-inflammatory and immunosuppressive stimuli through binding to their cognate receptors

• Cells expressing CCR5 contribute to an immune-suppressive tumor microenvironment and modulate immune response and tumor progression

• CCR5 stimulates oncogenic pathways, DNA repair and upregulation of antiapoptotic genes in cancer cells resulting in cancer cell proliferation, invasion and migration

• CCR5 is upregulated in many tumors and associated with poor outcome

• Promising efficacy results with CCR5 inhibitors have been observed in preclinical cancer models

• Clinical trials investigating the role of CCR5 antagonists in various malignancies are warranted to further improve our treatment against cancer

This box summarizes key points contained in the article.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer Disclosures

One of the reviewers on this paper is the founder with part ownership interest of a company that conducts clinical activities related to CCR5 therapeutics. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Additional information

Funding

This paper was not funded.