Modulation of graft-versus-tumor effects in a murine allogeneic bone marrow transplantation model by tumor-derived transforming growth factor-betaI.
Although graft-versus-leukemia effects in allogeneic bone marrow transplantation (alloBMT) are well documented, graft-versus-tumor (GVT) effects are poorly defined. To investigate the latter, we established a murine model of breast cancer using TS/A, a transforming growth factor (TGF)-beta1-secreting breast cancer cell line of BALB/c origin. In the setting of disparate (parent 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 line. Mice were inoculated with either TGF-beta1 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 survival between syngeneic and alloBMT groups. However, there was a highly statistically 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 of mice that received alloBMT for TGF-beta1 antisense-transfected tumor versus mock-transfected tumor (P = .0008). These data suggest that (1) GVT exists against the antisense-transfected breast cancer cells in this experimental model and (2) TGF-beta1 may be involved in suppressing antitumor responses in the setting of alloBMT for breast cancer.
Kummar
S
S
Experimental Immunology Branch, DBS, National Cancer Institute, National Insti- tutes of Health, Bethesda, Maryland 20892-1360, USA.
Ishii
A
A
Yang
H K
HK
Venzon
D J
DJ
Kim
S J
SJ
Gress
R E
RE
D000818:Animals; D016026:Bone Marrow Transplantation; D005260:Female; D020350:Graft vs Tumor Effect; D008325:Mammary Neoplasms, Experimental / Q000378:metabolism* / Q000473:pathology / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D016212:Transforming Growth Factor beta / Q000096:biosynthesis*; D053773:Transforming Growth Factor beta1; D014184:Transplantation, Homologous
C508961:Tgfb1 protein, mouse; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1