Role of PD-1 Ligand in Immune Evasion by Breast Cancer

摘要

The PD-1/PD-1 Ligand pathway inhibits T cell activation. We demonstrated expression of PD-L1 by immunohistochemistry on breast tumor cells in situ but PD-L1 was not expressed on normal breast epithelium. PD-L1 expression provides a mechanism whereby tumor cells can inhibit immune responses. We also demonstrated expression of PD-L1 in breast cancer cell lines. MDA231 has the highest PD-L1 expression among the cell lines tested. SKBR3, another breast cancer cell line, has the most PD-L2 expression. PD-L1 expression on MDA231 cells can be up-regulated by estrogen up to 50 microg/ml but there was no change in PD-L2 expression. We identified anti-PD-ligand antibodies with non-overlapping epitopes and developed an ELISA for detecting soluble PD-L1 in serum. In the small number of samples analyzed, there was no difference in soluble serum levels of PD-L1 between normal controls and breast cancer samples. Blockade of the PD-1/PD-1 Ligand pathway upregulated CD4(+) and CD8(+) allo-responses, in which either dendritic cells or MDA231 breast cancer cells were used as allo-stimulators. Blockade of the PD-1/PD-1 Ligand pathway also enhanced CD8 T cell IFN-gamma production and an increase in CD8 T cell number in an allo-response to MDA231 cells.