Myeloid-derived suppressor cells isolated from 4T1 tumor-bearing mice are only immunosuppressive under serum-free conditions (147.25)

Abstract

Abstract Myeloid-derived suppressor cells (MDSCs) are defined by their ability to suppress T cell responses. However, different in vitro culture conditions have been used to assay MDSC function, which may explain why some labs have been unable to demonstrate the suppressive nature of these cells. To address this, we isolated MDSCs from BALB/c mice bearing syngeneic 4T1 metastatic murine mammary tumors and compared the ability of these 4T1-MDSCs to suppress T cell proliferation under serum-containing (10% FCS) and serum-free conditions. Interestingly, we found that these MDSCs only suppressed T cell proliferation under serum-free conditions. Conversely, peritoneal macrophages and tumor-associated macrophages were able to effectively suppress T cell proliferation under both serum-free and serum-containing conditions. These results indicate that serum profoundly alters the immunosuppressive properties of 4T1-MDSCs. We investigated the components of serum responsible for inhibiting the suppressive phenotype of MDSCs and found that 4T1-MDSCs failed to suppress T cell proliferation in serum-free medium supplemented with bovine serum albumin (BSA), yet MDSC suppression in 10% FCS medium was restored when BSA was depleted from the serum. Taken together, these data highlight the importance of testing different in vitro culture conditions on MDSC phenotype to ensure that the presence of serum is not masking the immunosuppressive properties of MDSCs.