CXCR4 and colonic neoplasm: In the hypoxic state, the overexpression of hypoxia-inducible factors and activation of downstream signaling pathways (including CD47, CXCR4 and MAPK/ERK) can mediate immune escape in many ways, such as through the release of many immunosuppressive growth factors and cytokines [56, 57], upregulation of the negative immune checkpoint V-set immunoregulatory receptor in colon cancer [58], and induction of programmed cell death 1/programmed cell death 1 ligand 1 for T-cell inhibition [59, 60] and CD47 for macrophage suppression [61].