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

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...

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Bibliographic Details
Main Authors: Ma, Feng-Rong, Freeman, Gordon
Format: Report
Language:English
Subjects:
BLOOD SERUM
BREAST CANCER
CELL LINES
CELLS(BIOLOGY)
ENZYMES
EPITHELIUM
ESTROGENS
HISTOCHEMISTRY
IMMUNITY
IMMUNOASSAY
IMMUNOCHEMISTRY
IMMUNOHISTOCHEMISTRY
LIGANDS
MAMMARY GLANDS
Medicine and Medical Research
PD-1 LIGAND
RESPONSE(BIOLOGY)
SAMPLING
SOLUBILITY
T LYMPHOCYTES
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Summary: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. The original document contains color images.