Chemokine Offers Tempting Target in Tumor Niche

Jane De Lartigue, PhD
Published: Tuesday, Mar 19, 2019
The tumor microenvironment (TME) comprises a diverse array of immune cells recruited into the supportive niche that surrounds the tumor through interactions between chemokines and their cell surface receptors. Chemokine receptor type 2 (CCR2), a major recruiter of circulating monocytes that subsequently develop into a protumoral type of macrophage within the TME, has emerged as a promising therapeutic target.

The CCR2 signaling axis may also offer a way to overcome challenges for an established therapeutic strategy. Chimeric antigen receptor (CAR) T cells genetically engineered to express CCR2 could penetrate more readily into the TME, which has been a barrier to the antitumor efficacy of CAR T cells in solid tumors until now.

Masters of Migration

The cells of the immune system secrete a range of chemical messengers known as cytokines that facilitate communication with one another and the host. Chemokines are a subfamily of cytokines that specialize in mediating migration; they function as chemoattractants, providing directional cues for immune cells to recruit them to sites of inflammation where immune cells are needed for tissue defense and repair.

Figure. Chemokines in Action

Figure. Chemokines in Action There are several subgroups of chemokines, defined by the position of conserved cysteine amino acids within their structure; in the CC chemokines, there are 2 adjacent cysteines near the beginning of the protein.

Moving Monocytes

CCR2 functions predominantly as a receptor for chemokine ligand 2 (CCL2), an inflammatory CC chemokine, also known as monocyte chemoattractant protein-1, reflecting its major role in the regulation of monocyte migration to sites of pathologic inflammation.

A Cancer Hallmark

Tumors don’t exist in isolation; they are surrounded by host cells and tissues, with which they can interact. Tumor cells can use those interactions to manipulate their local microenvironment, creating a supportive niche. The TME fundamentally influences tumor biology and acts as a barrier to effective anticancer therapy.
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