CXCR4 and neoplasm: TAMs themselves are recruited into the TME by tumor-derived adenosine, the CCL2/CCR2 axis, the CXCL12/CXCR4 axis, and the VEGF receptor pathway; tumor cells, stromal cells, and macrophages are responsible for the production of chemokines necessary to attract TAMs and MDSCs into the TME (Qian et al., 2011; Hughes et al., 2015; Montalbán Del Barrio et al., 2016; Li X. et al., 2019).