title: Immune competence of cancer-reactive T cells generated de novo in adult tumor-bearing mice.
abstract: The impact of timing of antigen introduction into fetus and neonates leads to the suggestion that pre-existing antigens are tolerogenic to immunocompetent cells generated thereafter. This hypothesis predicts that in patients with cancer who are undergoing bone marrow transplantation, newly produced T cells with specificity for pre-existing tumor cells will be inactivated by the tumor antigens in the host. Because the effect of tumor cells on developing cancer-reactive T cells has not been investigated, we set out to systematically analyze the impact of tumor cells in the periphery on the development of tumor-reactive T cells in the thymus and their immunocompetence in the periphery. Our data demonstrate that in the host in which a tumor is established in the periphery, the cancer-reactive T cells develop normally, remain fully immunocompetent, become activated in the periphery, and cause regression of large established tumors. The immunocompetence of T cells generated in an antigen-bearing host is also confirmed in a skin graft transplantation model.
authors.affiliation: Division of Cancer Immunology, Department of Pathology, Ohio State University Medical Center and Comprehensive Cancer Center, Columbus, OH, USA.
authors.forename: Kenneth F
authors.initials: KF
authors.lastname: May
authors.forename: Kenneth
authors.initials: K
authors.lastname: Lute
authors.forename: Ergun
authors.initials: E
authors.lastname: Kocak
authors.forename: Shahab
authors.initials: S
authors.lastname: Abdessalam
authors.forename: Lijie
authors.initials: L
authors.lastname: Yin
authors.forename: Ou
authors.initials: O
authors.lastname: Li
authors.forename: Zhen
authors.initials: Z
authors.lastname: Guan
authors.forename: Gary
authors.initials: G
authors.lastname: Philips
authors.forename: Pan
authors.initials: P
authors.lastname: Zheng
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology*; D016026:Bone Marrow Transplantation; D017637:Clonal Deletion; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics; D007121:Immunocompetence; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D008822:Mice, Transgenic; D018448:Models, Immunological; D010954:Plasmacytoma / Q000276:immunology* / Q000628:therapy; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology; D012878:Skin Neoplasms / Q000276:immunology; D013047:Specific Pathogen-Free Organisms; D037182:T-Cell Antigen Receptor Specificity; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D014184:Transplantation, Homologous
chemical_list: D000951:Antigens, Neoplasm; D004268:DNA-Binding Proteins; C499308:Rag2 protein, mouse; D011948:Receptors, Antigen, T-Cell; C076546:tumor rejection antigen P815A, mouse