Studies of
tumor models using
syngeneic transplantation have advanced our understanding of
tumor immunity, including both immune surveillance and evasion. Murine mammary
carcinoma 4T1 cells secrete immunosuppressive soluble factors as demonstrated in splenocyte culture. Cultured primary splenocytes secrete IFN-γ, which was strikingly elevated when the cells were isolated from 4T1
tumor-bearing mice. The secretion of IFN-γ 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-γ 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-γ suppression is 4T1
tumor-specific. The soluble factor(s) in the 4T1-conditioned media was a
protein between 10 to 100 kDa. The
cytokine tip assay demonstrated several known
cytokines that negatively regulate immune responses and may be candidates for this immunosuppression activity.