CTLA-4: New insights into its biological function and use in tumor immunotherapy

Jackson G. Egen, Michael S. Kuhns, James P. Allison

Research output: Contribution to journalReview articlepeer-review

775 Scopus citations


The discovery of multiple costimulatory cell surface molecules that influence the course of T cell activation has increased our appreciation of the complexity of the T cell response. It remains clear, however, that CD28 and cytotoxic T lymphocyte antigen 4 (CTLA-4) are the critical costimulatory receptors that determine the early outcome of stimulation through the T cell antigen receptor (TCR). Details of how the T cell integrates TCR stimulation with the costimulatory signals of CD28 and the inhibitory signals of CTLA-4 remain to be established, but unique features of the cell biology of CTLA-4 provide important insights into its function. We summarize here recent findings that suggest a previously unrecognized role for CTLA-4 in the regulation of T cell responses. We also describe preclinical and clinical results that indicate manipulation of CTLA-4 has considerable promise as a strategy for the immunotherapy of cancer.

Original languageEnglish (US)
Pages (from-to)611-618
Number of pages8
JournalNature immunology
Issue number7
StatePublished - 2002

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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