BXD recombinant inbred mice represent a novel T cell-mediated immune response tumor model

To develop a better animal model for studying the effects of the host environment in neoplasia, we injected various genetically well-characterized H-2(d) RI strains of BXD mice with syngeneic breast cancer cells (TS/A) and monitored the growth of tumors over time. There was a marked difference in the growth of the implanted breast cancer cells among the 14 BXD RI strains, with 4 patterns of tumor development being observed: in type I, the implanted tumor cells grew rapidly in the first 2 weeks, necrosis of the tumors was observed and metastases to the intestinal lymph nodes and pancreas was observed, causing death; in type II, the implanted tumor cells grew slowly and attained a size after day 50 that required killing the animal, with tumor necrosis being rare and metastases absent; in type III, the implanted tumor cells grew initially but underwent a slow decline after 4 weeks; and in type IV, the implanted tumor cells failed to develop. Apoptosis of the implanted tumor cells was responsible for the regression of tumor nodules. The T-cell immune response minimized tumor development in types III and IV since T-cell depletion of the BXD RI mice resulted in aggressively growing tumors in these strains.