Chemokine (C-C motif) receptors 2 (CCR2) and 5 (CCR5) can promote trafficking of immunosuppressive cells and suppress T-cell function. CCR2/CCR5 inhibition may decrease tumor infiltration of these immunosuppressive cells.
- CCR2 and CCR5 are both expressed on T cells, Tregs, monocytes, MDSCs, and TAMs1-6
- CCR2 and CCR5 regulate the recruitment of immunosuppressive cells through the stroma7,8
- The ligands for CCR2 and CCR5 are chemokine (C-C motif) ligand 2 (CCL2) and 5 (CCL5), respectively3,7
- CCL2 and CCL5, expressed by tumor and stromal cells, promote the trafficking and infiltration of immunosuppressive Tregs, TAMs, and MDSCs, by interacting with the CCR2 and CCR5, respectively, on these
- Tumors use CCR2 signaling to mobilize inflammatory monocytes from the bone marrow into the blood and to sites of inflammation, where they infiltrate the tumor microenvironment9,11,12
- These monocytes can differentiate into protumor macrophages, such as TAMs, that suppress
cytotoxic T-cellproliferation and function.9,11,12
- CCR5 can stimulate the differentiation of monocytes into protumor TAMs as well as induce MDSC differentiation7
- CCR2, CCR5, and their ligands may be elevated in certain advanced solid tumors and may enhance tumor cell survival9,13,14
- Preclinical data suggest that depletion or blockade of CCR2 and CCR5, individually or in combination, decreases the infiltration of MDSCs, TAMs, and Tregs into the tumor microenvironment10,11,15-17
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1. de Oliveira CEC, Oda JMM, Guembarovski RL, et al. CC chemokine receptor 5: the interface of host immunity and cancer. Dis Markers. 2014;2014:126954. doi:10.1155/2014/126954. 2. Lesokhin AM, Hohl TM, Kitano S, et al. Monocytic CCR2+ myeloid-derived suppressor cells promote immune escape by limiting activated CD8 T-cell infiltration into the tumor microenvironment. Cancer Res.