Modulation of graft-versus-tumor effects in a murine allogeneic bone marrow transplantation model by tumor-derived transforming growth factor-beta 1

Although graft-versus-leukemia effects in allogeneic bone marrow transplant ation (alloBMT) are well documented, graft-versus-tumor (GVT) effects are p oorly defined. To investigate the latter, we established a murine model of breast cancer using TS/A, a transforming growth factor (TGF)-beta1-secretin g breast cancer cell line of BALB/c origin. In the setting of disparate (pa rent into F1) alloBMT, no appreciable GVT was identified. To assess whether TGF-beta1 secreted by the tumor might inhibit the antitumor response, TGF- beta1 antisense vector was transfected into the TS/A breast cancer cell lin e. Mice were inoculated with either TGF-betaL antisense transfected or the mock transfected cell line and underwent syngeneic or alloBMT, No evidence of GVT was appreciated for the mock-transfected breast cancer cell line as assessed by an absence of a statistically significant difference in surviva l between syngeneic and alloBMT groups. However, there was a highly statist ically significant survival difference between allogeneic versus syngeneic bone marrow transplantation groups inoculated with the TGF-beta1 antisense- transfected cell line (P = .00001) as well as when comparing the survival o f mice that received alloBMT for TGF-beta1 antisense-transfected tumor vers us mock-transfected tumor (P = .0008). These data suggest that (1) GVT exis ts against the antisense-transfected breast cancer cells in this experiment al model and (2) TGF-betaI may be involved in suppressing antitumor respons es in the setting of alloBMT for breast cancer.