Fig. 6

M2 polarization of TAMs facilitates immunosuppression through the elevated expression of PD-L2. a THP-1 monocyte is induced into M1-type by LPS and IFN-γ, and into M2-type by IL-4 and IL-13 following PMA treatment. The polarized M1 and M2 macrophages were distinguished from inactive M0 macrophage with the biomarker HLA-DR and CD209, respectively. b Flow cytometry analysis shows discrepant expression of PD-L1 and PD-L2 between HLA-DR⁺CD209⁻ M1 macrophages and HLA-DR⁻CD209⁺ M2 macrophages. Data is shown by mean ± standard deviation from three independent experiments. When compared to the control group, * indicates P < 0.05, ** indicates P < 0.01. c PD-L2 expression is higher in M2 (F4/80⁺CD206⁺) than M1 (F4/80⁺CD206⁻) macrophages in ESCC mouse model (n = 5). d Blockade of CCL2-CCR2 axis in animal models reduces expression of PD-L2 during carcinogenesis (n = 5). e Pearson correlation analysis with TCGA data indicates strong association of PD-L2 with CCL2 expression and the level of M2 marker CD209 in human ESCC