The development of peritumoral stroma required for IL-12 induced tumor regression depends on the T cell/IFN-gamma-involving host-tumor interaction

T cell migration into tumor masses is a critical process in the scenario of IL-12-induced tumor regression. Our previous study showed that this depend s on the development of peritumoral stroma prior to IL-12 therapy. The pres ent study investigated the regulation of the development of peritumoral str oma in comparison with tumor-parenchymal stroma. In the OV-HM and CSA1M tum or models, tumor regression associated with T cell migration was induced fo llowing IL-12 treatment. Both OV-HM and CSA1M tumor masses growing in synge neic mice developed peritumoral stroma before IL-12 treatment. However, per itumoral stroma was not observed in these two types of tumor masses generat ed in nude mice, T cell-depleted syngeneic mice, anti-IFN-gamma mAb-treated mice or IFN-gamma-deficient mice. In contrast, parenchymal stroma formatio n did not appear to be affected because tumors generated in these groups of mice exhibited rather higher growth rates than those of tumors in normal s yngeneic mice. Importantly, the lack of peritumoral stroma in tumor masses was associated with the failure of T cells to migrate to these tumor masses : splenic T cells prepared from IL-12-treated tumor-bearing mice migrated i nto the corresponding tumor mass growing in untreated syngeneic recipient m ice, whereas portions of the same donor cells failed to migrate into the ab ove stroma-negative tumor masses. These results indicate that the developme nt of peritumoral and parenchymal stroma is differentially regulated; there exist functional differences in the two types of stroma; and the formation of peritumoral stroma requires components of the host's immune system such as IFN-gamma and T cells.