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Age-dependent tolerance to an endogenous tumor-associated antigen

Authors
Journal
Vaccine
0264-410X
Publisher
Elsevier
Publication Date
Volume
26
Issue
15
Identifiers
DOI: 10.1016/j.vaccine.2008.01.052
Keywords
  • Tumor-Associated Antigen
  • Immunologic Tolerance
  • Immunosurveillance
Disciplines
  • Medicine

Abstract

Summary 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.

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