In vivo blockade of CTLA-4 enhances the priming of responsive T cells but fails to prevent the induction of tumor antigen-specific tolerance

Eduardo M. Sotomayor, Ivan Borrello, Erev Tubb, James P. Allison, Hyam I. Levitsky

Research output: Contribution to journalArticle

Abstract

The efficacy of therapeutic vaccination for the treatment of cancer is limited by peripheral tolerance to tumor antigens. In vivo blockade of CTLA- 4, a negative regulator of T cell function, can induce the regression of established tumors and can augment the tumor rejection achieved through therapeutic vaccination. These outcomes may reflect enhanced tumor-specific T cell priming and/or interference with the development of tolerance to tumor antigens. We examined the effect of CTLA-4 blockade on the fate and function of T cells specific for a model tumor antigen in the tumor-bearing host. We found that while CTLA-4 blockade enhanced the priming of responsive T cells, it did not prevent the induction of tolerance to tumor antigens. These results demonstrate that there is a critical window in which the combination of CTLA-4 blockade and vaccination achieves an optimal response, and they point to mechanisms other than CTLA-4 engagement in mediating peripheral T cell tolerance to tumor antigens.

Original languageEnglish (US)
Pages (from-to)11476-11481
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume96
Issue number20
DOIs
StatePublished - Sep 28 1999

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