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

Nat Immunol. 2002 Jul;3(7):611-8. doi: 10.1038/ni0702-611.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Abatacept
  • Animals
  • Antigens, CD
  • Antigens, Differentiation / genetics
  • Antigens, Differentiation / immunology*
  • Antigens, Differentiation / therapeutic use
  • CTLA-4 Antigen
  • Cell Division
  • Colonic Neoplasms / therapy
  • Disease Models, Animal
  • Fibrosarcoma / therapy
  • Gene Expression Regulation
  • Humans
  • Immunoconjugates*
  • Immunotherapy* / methods
  • Lymphocyte Activation
  • Mice
  • Neoplasms / immunology
  • Neoplasms / therapy*
  • T-Lymphocytes / immunology


  • Antigens, CD
  • Antigens, Differentiation
  • CTLA-4 Antigen
  • CTLA4 protein, human
  • Ctla4 protein, mouse
  • Immunoconjugates
  • Abatacept