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J Clin Invest. 2003 May;111(10):1487-96.

Antigenic drift as a mechanism for tumor evasion of destruction by cytolytic T lymphocytes.

Author information

1
Division of Cancer Immunology, Department of Pathology, Ohio State University Medical Center, Columbus, Ohio 43210, USA.

Abstract

It is established that mutations in viral antigenic epitopes, or antigenic drifts, allow viruses to escape recognition by both Ab's and T lymphocytes. It is unclear, however, whether tumor cells can escape immune recognition via antigenic drift. Here we show that adoptive therapy with both monoclonal and polyclonal transgenic CTLs, specific for a natural tumor antigen, P1A, selects for multiple mutations in the P1A antigenic epitope. These mutations severely diminish T cell recognition of the tumor antigen by a variety of mechanisms, including modulation of MHC:peptide interaction and TCR binding to MHC:peptide complex. These results provide the first evidence for tumor evasion of T cell recognition by antigenic drift, and thus have important implications for the strategy of tumor immunotherapy.

PMID:
12750398
PMCID:
PMC155049
DOI:
10.1172/JCI17656
[Indexed for MEDLINE]
Free PMC Article

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