Macrophages Upregulate PD-L1 Expression On Human Breast Cancer Cells

BackgroundMacrophages are distributed in tissues throughout the body.Recently,it has become evident that most adult tissue macrophages originate during embryonic development,aside from circulating monocytes.Macrophages mediate innate immune responses and contribute to adaptive immunity via antigen processing.Macrophages play a “double-edged sword” role in tumor progression due to macrophage plasticity.At the beginning of the tumorigenesis,macrophages can identify and eliminate tumor cell,but with the progress of the tumor,macrophages are polarized to tumor associated macrophages(TAM),promote tumor to invasion and metastasis.PD-L1 in the tumor tissues interactation with PD-1 on tumor infiltrating T lymphocytes(TILs)can induce TILs apoptosis and “dysfunctional”,as an key means of tumor escape.numbers of factors in the tumor microenvironment are involved in upregulation of PD-L1 on tumor cells.It is of great significance to clarify how macrophages affect PD-L1 expression on tumor cells.ObjectivesTo explore whether macrophages can induce PD-L1 expression on human breast cancer cells,and the related signaling pathway.MethodsWe generated M1/M2 polarized macrophages by treating THP-1 cells with PMA for 6 hours and polarizing them with IFN-? and LPS for 18 hours,or polarizing them with IL-4 and IL-13 for 18 h.Then we use M1/M2 polarized macrophages to coculture with human breast cancer cells in noncontact system.Further,we test PD-L1 expression on breast cancer cells,and explore the change of cytokines in M1-polarized macrophages and explicit the signaling pathway in breast cancer cells.Results1.We generated M1/M2 polarized macrophages by treating THP-1 cells with PMA for 6 hours and polarizing them with IFN-? and LPS for 18 hours,or polarizing them with IL-4 and IL-13 for 18 h.2.M1/M2 polarized macrophages could upregulate PD-L1 expression of MCF-7 cells and SKBr3 cells,M1-polarized macrophages could induce more PD-L1 expression on human breast cancer cells than M2-polarized macrophages.3.IFN-?,secreted by M1-polarized macrophages,active JAK-Stat1 signaling pathway of MCF-7 cells to upregulate PD-L1 expression.The overexpression of PD-L1 induced by M2-polarized macrophages was not dependent on STAT3 signal pathways in Breast cancer cells.ConclusionsM1/M2 polarized macrophages could upregulate PD-L1 expression on breast cancer cells.IFN-?,secreted by M1-polarized macrophages,active JAK-Stat1 signaling pathway of MCF-7 cells to upregulate PD-L1 expression.