Fig. 8. Schematic representation of synergistic effects of CCR1 and CXCR2 in CRC progression.

In the TME of CRC, both CCR1 ligands (e.g., human CCL15 and mouse CCL9) and CXCR2 ligands (e.g., CXCL1 and human CXCL8) secreted from CRC cells recruits CCR1⁺ and/or CXCR2⁺ neutrophils from blood vessels. Thereafter, these recruited neutrophils promote tumor progression through immunosuppressive function (by decreasing CD8⁺ T cells and increasing regulatory T cell) and tissue-destructive and angiogenic function (by producing MMP2, MMP9 and VEGF). Created with BioRender.com.