The balance between
inflammation and immunity is cardinal for the outcome of the malignant process. Local attenuated inflammatory responses mediated by innate cells may provide accessory signals for the development of acquired immunity against malignant cells. In contrast, excessive inflammatory responses accompany
tumorigenesis and
tumor invasiveness, by the induction of immunosuppression. In the present study, we have assessed the role of
tumor cell-derived
IL-1 in determining the invasive versus immunostimulatory potential of
tumor cells. For this purpose, we have used 3-MCA-induced
fibrosarcoma cell lines from
IL-1 knockout (KO) versus control mice. Cell lines with no
IL-1 failed to establish
tumors in intact mice, while lines obtained from control mice were invasive and induced a potent angiogenic response. In contrast, cell lines from IL-1KO mice were more immunogenic. SDF-1 and
IL-6, each induced by
IL-1, were the two major
cytokines whose levels differed in cell lines with or without
IL-1. We could not detect differences in cell surface markers related to immunogenicity, such as MHC Class I, co-stimulatory, or adhesion molecules between both types of cells. However, more T-cells were observed at the inoculation site of
tumor cells devoid of
IL-1 and more pronounced parameters related to anti-
tumor immunity were observed in the spleen (
IL-12 and IFNgamma) of these mice, compared to mice bearing
tumors derived from control mice, where host-derived
IL-1 is present. In addition, injection of
tumor cells devoid of
IL-1, which failed to grow in mice, induced an anti-
tumor cell immune memory, while in mice injected with
tumor cells from control mice; no immune memory could be detected. From the results, it seems that
IL-1 is a crucial factor in determining the balance between immunity and
inflammation in
tumor-bearing mice. This suggests that manipulation of
IL-1 could be useful in anti-
tumor therapy, by reducing invasiveness and promoting immunity against the malignant cells.