Reduction of the number and/or suppressive mechanisms of myeloid cells by mammary tumor cells expressing a secreted isoform of MUC1 (50.10)

Abstract

Abstract Expression of the transmembrane isoform of MUC1 (MUC1/TM) in an aggressive murine mammary tumor line, DA-3, results in tumor development leading to metastasis and death of the host, as does the untransfected parental tumor line. However, tumor cells expressing a secreted isoform of MUC1 (MUC1/sec) fail to develop tumors in vivo. The rejection of tumors was found to be immunologically mediated, as initially innate cells and ultimately T cells are required. Previous work to determine which lymphoreticular cells may be involved in the immune rejection revealed that MUC1/sec expressing cells recruited four times the amount of F4/80+ cells, while recruiting significantly lower numbers of GR-1+ cells, relative to MUC1/TM expressing tumor cells. Gr-1+CD11b+ cells known as immature Myeloid Derived Suppressor Cells (MDSC) have been correlated with immune suppression in many models of cancer and chronic infections. MDSC accumulate in response to MUC1/TM expressing tumor cells, but remaine at normal levels in animals exposed to MUC1/sec expressing tumor cells. Futhermore, supernatants from MUC1/sec expressing tumor cells blocked induction of arginase in MDSC, a mechanism of suppression. This block in induction of arginase could also be demonstrated by use of a unique peptide, Immuno Enhancing Peptide, only found in the MUC1/sec protein. NIH, NCI R01CA25583.