Establishment and control of the L5178Y-cell tumor dormant state in DBA/2 mice

Abstract

The L5178Y-cell tumor dormant state in DBA/2 mice is an excellent model for assessing immunologically mediated tumor-growth restraint mechanisms associated with establishment and control of a tumor dormant state. It has enabled us to relate components of the host's tumor suppressive immune system to the stage of tumor dormancy and the magnitude of the tumor burden. A strong CTL response has been associated with establishment of the tumor dormant state and can be reelicited in vivo or in vitro, after its initial decline, by reexposure to tumor antigen. This reelicitation is mediated via immunologic stimulation of memory CTL. Combined cultures of NAD T-lineage lymphocytes and macrophages from tumor dormant mice produce considerable cytolytic activity where little or no activity can be detected in the individual populations. Based on the similar pattern of tumor target cell specificity of the two responses, it is likely that memory CTL contribute to this synergistic cytolytic activity. The synergistic cytolytic response persists after CTL activity has waned to undetectable levels and is probably the predominant cytolytic activity associated with maintenance of the tumor dormant state. However, this activity may be obscured by proliferation of endogenous tumor cells, which in turn triggers direct macrophage-mediated cytolytic activity. The target cell specificity of this direct macrophage-mediated cytolytic response is also similar to the CTL response suggesting T cell (or memory CTL) involvement in its generation. The L5178Y-cell tumor dormant model is well suited for attempts at cure with immunotherapy. Active specific and nonspecific immunotherapy are each capable of eliminating all tumor cells from approximately 50% of tumor dormant mice. The L5178Y-cell tumor dormant state is one of several animal models of tumor dormancy. The great variety of growth restraint mechanisms that control tumor dormant states in animal systems is strong evidence that tumor dormant states exist in cancer in human beings.