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CCR2/CCR5
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 TAMs
1-6
- CCR2 and CCR5 regulate the recruitment of immunosuppressive cells through the stroma
7,8
- 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
cells.2,3,6-8,10,11
- 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-cell proliferation 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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REFERENCES–CCR2/CCR5
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.