Several studies have also shown that high doses of anti-angiogenic agents could lead to hypoxia of the tumor microenvironment and upregulation of the CXCR4/CXCL12 axis and HIF-α levels due to excessive pruning of tumor vessels, which facilitates the recruitment of TAMs, MDSCs, and Tregs (Figure 2C) (119, 120). Here, CXCL12 is linked to neoplasm.