Age-dependent tolerance to an endogenous tumor-associated antigen.
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.
McWilliams
Jennifer A
JA
Integrated Department of Immunology, University of Colorado, Denver.
Sullivan
Richard T
RT
Integrated Department of Immunology, University of Colorado, Denver.
Jordan
Kimberly R
KR
Integrated Department of Immunology, University of Colorado, Denver.
McMahan
Rachel H
RH
Integrated Department of Immunology, University of Colorado, Denver.
Kemmler
Charles B
CB
Integrated Department of Immunology, University of Colorado, Denver.
McDuffie
Marcia
M
Department of Microbiology, University of Virginia School of Medicine.
Slansky
Jill E
JE
Integrated Department of Immunology, University of Colorado, Denver.
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
D000951:Antigens, Neoplasm