Age-dependent tolerance to an endogenous tumor-associated antigen

• Published in: Vaccine Vol. 26; no. 15; pp. 1863 - 1873
• Main Authors: McWilliams, Jennifer A, Sullivan, Richard T, Jordan, Kimberly R, McMahan, Rachel H, Kemmler, Charles B, McDuffie, Marcia, Slansky, Jill E
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 28.03.2008; Elsevier; Elsevier Limited
• Subjects: Aging - immunology; Allergy and Immunology; Animal tissues; Animals; Antigens; Antigens, Neoplasm - immunology; Biological and medical sciences; Colonic Neoplasms - immunology; Female; General aspects (metabolism, cell proliferation, established cell line...); Immune system; Immune Tolerance; Immunologic tolerance; Immunosurveillance; Immunotherapy; Male; Medical research; Medical sciences; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Knockout; Rodents; T cell receptors; T-Lymphocytes - immunology; Tumor cell; Tumor-associated antigen; Tumors; Tumor-associated antigen; Immunosurveillance; Immunologic tolerance; Vertebrata; Mammalia; Endogenous; Tumor associated antigen; Mouse; Rodentia; Age
• ISSN: 0264-410X; 1873-2518
• DOI: 10.1016/j.vaccine.2008.01.052

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.