Accumulation of CD8+ T cells in advanced-stage tumors and delay of disease progression following secondary immunization against an immunorecessive epitope.
Self-reactive T cells that survive the process of positive and negative selection during thymocyte development represent potential effector cells against tumors that express these same self-Ags. We have previously shown that CD8+ T lymphocytes (T(CD8)) specific for an immunorecessive epitope, designated epitope V, from the SV40 large T Ag (Tag) escape thymic deletion in line SV11 Tag-transgenic mice. In contrast, these mice are tolerant to the three most dominant Tag epitopes. The majority of the residual epitope V-specific T(CD8) have a low avidity for the target epitope, but a prime/boost regimen can expand higher avidity clones in vivo. Whether higher avidity T(CD8) targeting this epitope are affected by Tag-expressing tumors in the periphery or can be recruited for control of tumor progression remains unknown. In the current study, we determined the fate of naive TCR-transgenic T(CD8) specific for Tag epitope V (TCR-V cells) following transfer into SV11 mice bearing advanced-stage choroid plexus tumors. The results indicate that TCR-V cells are rapidly triggered by the endogenous Tag and acquire effector function, but fail to accumulate within the tumors. Primary immunization enhanced TCR-V cell frequency in the periphery and promoted entry into the brain, but a subsequent booster immunization caused a dramatic accumulation of TCR-V T cells within the tumors and inhibited tumor progression. These results indicate that epitope V provides a target for CD8+ T cells against spontaneous tumors in vivo, and suggests that epitopes with similar properties can be harnessed for tumor immunotherapy.
Ryan
Christina M
CM
Department of Microbiology and Immunology, Pennsylvania State University College of Medicine, 500 University Drive, Hershey, PA 17033, USA.
Schell
Todd D
TD
D019264:Adoptive Transfer; D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000008:administration & dosage / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D001932:Brain Neoplasms / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000517:prevention & control; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology* / Q000637:transplantation; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics / Q000276:immunology; D002831:Choroid Plexus / Q000276:immunology / Q000473:pathology; D003601:Cytotoxicity Tests, Immunologic; D018450:Disease Progression; D018984:Epitopes, T-Lymphocyte / Q000008:administration & dosage / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D005260:Female; D005808:Genes, Recessive / Q000276:immunology; D007117:Immunization, Secondary / Q000379:methods; D008213:Lymphocyte Activation / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009367:Neoplasm Staging; D027601:Polyomavirus Infections / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000517:prevention & control*; D017434:Protein Structure, Tertiary / Q000235:genetics; D011948:Receptors, Antigen, T-Cell / Q000235:genetics; D016019:Survival Analysis; D014412:Tumor Virus Infections / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000517:prevention & control*
D000952:Antigens, Polyomavirus Transforming; D019496:Cancer Vaccines; D018984:Epitopes, T-Lymphocyte; D011948:Receptors, Antigen, T-Cell