MCP-1-CCR2-M2 macrophages axis contributes to diffuse large B-cell lymphoma progression and inhibits antitumor immune response

Diffuse large B-cell lymphoma (DLBCL) is an aggressive hematological malignancy with restricted effective therapy choices. The MCP-1/CCR2 axis is required for the recruitment of monocytes and polarization of macrophages. We investigated the feasibility of treatment targeting MCP-1-CCR2-macrophages axis in DLBCL. MCP-1, CD68, CD163 expression was analyzed by immunohistochemistry in 143 DLBCL patients tissues, and MCP-1 concentration and CD14+CCR2+ monocytes in peripheral blood were analyzed in another cohort by enzyme linked immunosorbent assay or flow cytometry. THP-1 or U937 cells were used to mimic macrophages polarization with or without the blockade of MCP-1/CCR2 axis in vitro. BALB/C mice subcutaneous tumors were evaluated and detected after blocking MCP-1/CCR2 axis with CCR2 antagonist. MCP-1, CD68, CD163 expression and proportion of CD14+CCR2+ monocytes in peripheral blood are prognostic for DLBCL patients. MCP-1 expression is positively associated with CD68 or CD163 expression in DLBCL. Blockade of MCP-1/CCR2 axis with CCR2 antagonist inhibits monocytes recruitment and M2 macrophages polarization in vitro and concomitantly increases the number of CD8 T-cells, which can lead to inhibition of subcutaneous tumour growth. MCP-1-CCR2-M2 macrophages polarization plays vital roles in DLBCL progression. The results demonstrate the translational potential of MCP-1/CCR2 blockade for treatment of DLBCL.