Studies of the mechanisms for the induction of in vivo tumor immunity. VII. Development of specific antitumor immunity in progressors and regressors

Abstract

The present study was aimed at comparing the development of specific antitumor immunity between hosts with progressively growing tumors and hosts with regressing tumors. The experiments were performed with a Friend virus-induced leukemia FBL-3 in syngeneic C57BL/6 mice. The specific antitumor immunity was determined by in vitro cell-mediated cytotoxicity assay and in vivo tumor neutralization test. Both the systemic immunity (demonstrated in spleen) and immunity developed at tumor site were examined. For progressors, the tumor site was in the peritoneal cavity. For regressors, it was in a subcutaneous site of both flanks. Testing by the cell-mediated cytotoxicity assay showed that immune hosts and regressors had higher levels of systemic immunity than the progressors. However, when lymphocytes isolated from tumor sites were assayed, it was found that there was no remarkable difference between lymphocytes from progressor tumors (PTL) and lymphocytes from regressor tumors (RTL). Both lymphocyte populations were similar in profile analysis; they were characterized as T cells and possessed the same antigenic specificity. Nevertheless, when in vivo tumor transplantation experiments were performed, RTL were found to give protection against FBL-3 challenge whereas PTL consistently failed to do so. On cytomorphological examination, the PTL were seen to contain large amounts of macrophages. The presence of macrophages in PTL appeared to have an inverse relationship to the in vivo protective effect. After removal of macrophages from PTL by Petri dish adherence, the nonadherent PTL were found to give in vivo protection. Furthermore, thymocytes from progressors and macrophages isolated from the progressor tumors were found to suppress the in vivo T-cell-mediated immunity. These findings demonstrated that suppressor T cells and suppressor macrophages were present in tumor-bearing hosts. These suppressor cells could interfere with the function of immune T cells at the efferent arm of the immune response.