Characterization of L5178Y cell phenotypes isolated during progression of the tumor-dormant state in DBA2 mice.
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 tumor-dormant 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.
D000818:Animals; D003602:Cytotoxicity, Immunologic; D005260:Female; D006183:H-2 Antigens / Q000032:analysis; D007940:Leukemia L5178 / Q000276:immunology* / Q000503:physiopathology; D007942:Leukemia, Experimental / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D010641:Phenotype; D013601:T-Lymphocytes / Q000276:immunology
D006183:H-2 Antigens