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Murine mammary carcinoma 4T1 cells secrete immunosuppressive soluble factors as demonstrated in splenocyte culture. Cultured primary splenocytes secrete IFN-\u03b3, which was strikingly elevated when the cells were isolated from 4T1 tumor-bearing mice. The secretion of IFN-\u03b3 peaked a week after 4T1 inoculation and then declined. This reduction may be due to the relatively decreased lymphocytes and increased granulocytes in a spleen accompanied by splenomegaly with time after the 4T1 inoculation. IFN-\u03b3 production was further suppressed with the addition of the conditioned media from 4T1 cells to the splenocyte culture. This suppressive effect was more evident in the splenocytes isolated from mice that had 4T1 tumors for a longer period of time and was not observed in the conditioned medium either from CT26 cells or with splenocytes isolated from CT26 tumor-bearing mice. These results suggest that the IFN-\u03b3 suppression is 4T1 tumor-specific. The soluble factor(s) in the 4T1-conditioned media was a protein between 10 to 100\u2005kDa. 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