In this study, through the first investigation of the relationship between PGRN and PD-L1 on macrophages, we have found a new role of PGRN to promote breast cancer progression, that is inducing M2 polarization and up-regulating PD-L1 through PGRN/STAT3, and then promoting CD8+ T cell exclusion and inhibiting tumor immunity through PD-1/PD-L1 interaction. This evidence concerns the gene GRN and breast cancer.