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Characterization of L5178Y Cell Phenotypes Isolated during Progression of the Tumor-dormant State in DBA/2 Mice¹

Department of Pathology and Laboratory Medicine, Hahnemann University, Philadelphia, Pennsylvania 19102

During the course of the L5178Y tumor-dormant state in DBA/2 mice, there is continual selection of a tumor cell subpopulation ("emergent" phenotype) from the uncloned original L5178Y population used to initiate the tumor-dormant state. In vivo and in vitro experiments show that the emergent-phenotype tumor cells are less capable than "original"-phenotype cells, which constitute the majority of the L5178Y cell inoculum, of restimulating cytolytic T-lymphocyte (CTL) activity in tumor-dormant mice and are less susceptible to lysis by those CTL. Both original- and emergent-phenotype tumor cells are capable of eliciting an immune CTL response in naive mice, but again emergent-phenotype cells are poorly lysed by this response. As a consequence of these characteristics, emergent-phenotype cells rapidly form ascitic tumors when used as a challenge in L5178Y cell-immunized mice and cannot establish a tumordormant state. Results presented here and in previous publications indicate that CTLs are the major host cells involved in the selection of emergent-phenotype L5178Y cells during the course of the tumor-dormant state.

Heterogeneity of the tumor cell challenge inoculum is important in establishing the L5178Y tumor-dormant state. The state, once established, is maintained by an immune CTL response which is continuously being restimulated by the strongly immunogenic original-phenotype L5178Y cells. The tumor-dormant state terminates when the less immunogenic and more immunoresistant emergent-phenotype tumor cells predominate and escape the waning immune response.

¹ Supported by Grant CA32577 awarded by the National Cancer Institute, Department of Health and Human Services.

² To whom requests for reprints should be addressed.

Received 5/27/83. Accepted 4/ 6/84.