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Vaccine. 2008 Mar 28;26(15):1863-73. doi: 10.1016/j.vaccine.2008.01.052. Epub 2008 Feb 20.

Age-dependent tolerance to an endogenous tumor-associated antigen.

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  • 1Integrated Department of Immunology, University of Colorado Health Sciences Center, 1400 Jackson Street, Denver, CO 80206, United States.

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.

PMID:
18329760
PMCID:
PMC2295286
DOI:
10.1016/j.vaccine.2008.01.052
[PubMed - indexed for MEDLINE]
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