A time factor in the success or failure of immune rejection of transplanted tumors

Changes in susceptibility to immune rejection have been studied and compared during the initial stages of s.c. and pulmonary establishment of a transplanted syngeneic C3H mouse mammary carcinoma. The time of immunological attack on the implanted tumor cells was varied by two experimental procedures: In one experiment, the test mice that were immunologically suppressed by the presence of a large s.c. tumor implant were surgically cured before s.c. challenge. However, the immune recovery, which normally follows directly after tumor removal, was delayed for increasing lengths of time after challenge by injections of irradiated cells of the same tumor. In another experiment, the test mice were immunologically impaired by sublethal whole-body irradiation before s.c. and i.v. challenge. Immune rejection reactivity was then introduced, by passive transfers of lymph node cells from immunized mice, at increasing delays after the challenge implantations of tumor cells. In both of the two experiments, an increase in the number of tumor "takes" was observed if tumor immunity was reduced or absent for at least 3 days after challenge. If tumor immunity was restored or provided by the third day after challenge, there was an abrupt decrease in the number of observed tumors. The reduction in the effectiveness of immunosupportive treatments about the third day after tumor implantation may indicate a reduction in the vulnerability to immune rejection that coincides with vascularization of the implants.