Figure 1.

Model showing the central role of CD14⁺ M2-macrophage-like cells in the immune suppression in cervical cancer. CD14⁺ monocytes are recruited from the peripheral blood by tumor-derived CCL2, produced by metastasizing tumor cells. In the presence of interleukin (IL)-6 and prostaglandin-E2 (PGE2), these monocytes become converted in the microenvironment of the tumor-draining lymph nodes and the primary tumor into CD14⁺ M2-macrophages expressing programmed death-ligand 1 (PD-L1). These suppressive CD14⁺ M2-macrophages promote progression and early metastasis of the primary tumor by producing pro-angiogenic and tumor-invasive factors. In addition, they can bind to PD-1 on antitumor effector T cells, thereby inhibiting an immune response against the primary and metastatic tumor cells. This immunosuppressive cycle is further amplified by the interplay and crosstalk of regulatory T cells (Treg) and myeloid-derived suppressor cells (MDSC).