title: Age-dependent tolerance to an endogenous tumor-associated antigen.
abstract: Immunologic tolerance to endogenous antigens reduces antitumor responses. Gp70 is an endogenous tumor-associated antigen (TAA) of the BALB/c-derived colon carcinoma CT26. We found that expression of gp70 mRNA is detectable in tissues of mice 8 months of age and older. We showed that expression of gp70 establishes immunologic tolerance and affects antitumor immunity in a similarly age-dependent manner using gp70-deficient mice. We found that tumors grew in all gp70-sufficient mice, while approximately half of gp70-deficient mice controlled tumor growth with endogenous T-cell responses. Protection in gp70-deficient mice correlated with more robust gp70-specific CTL responses, and increased numbers and avidity of responding antigen-specific T cells after vaccination. We conclude that immunosurveillance may decline with age due to increased or de novo peripheral expression of endogenous TAAs.
authors.affiliation: Integrated Department of Immunology, University of Colorado, Denver.
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: McWilliams
authors.affiliation: Integrated Department of Immunology, University of Colorado, Denver.
authors.forename: Richard T
authors.initials: RT
authors.lastname: Sullivan
authors.affiliation: Integrated Department of Immunology, University of Colorado, Denver.
authors.forename: Kimberly R
authors.initials: KR
authors.lastname: Jordan
authors.affiliation: Integrated Department of Immunology, University of Colorado, Denver.
authors.forename: Rachel H
authors.initials: RH
authors.lastname: McMahan
authors.affiliation: Integrated Department of Immunology, University of Colorado, Denver.
authors.forename: Charles B
authors.initials: CB
authors.lastname: Kemmler
authors.affiliation: Department of Microbiology, University of Virginia School of Medicine.
authors.forename: Marcia
authors.initials: M
authors.lastname: McDuffie
authors.affiliation: Integrated Department of Immunology, University of Colorado, Denver.
authors.forename: Jill E
authors.initials: JE
authors.lastname: Slansky
mesh_terms: D000375:Aging / Q000276:immunology*; D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology*; D003110:Colonic Neoplasms / Q000276:immunology*; D005260:Female; D007108:Immune Tolerance; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D000951:Antigens, Neoplasm