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

Nature Immunology volume 3, pages 611–618 (2002)Cite this article

Abstract

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.

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Figure 1: A model for CTLA-4 trafficking during antigen-specific T cell–APC interactions.
Figure 2: Role played by CTLA-4 in regulating antigen-specific T cell responses.
Figure 3: Modulation of T cell responses to tumors with CTLA-4 blockade.

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Acknowledgements

We thank P. Savage and J. Engelhardt for helpful discussions and critical reading of the manuscript and T. Sullivan, M. Fasso, C. Chambers, A. Hurwitz, A. van Elsas and E. Kwon for helpful discussions. Supported by the Howard Hughes Medical Institute and grants from the NIH (NCI CA40041 and CA57986) and CaPCURE (J. P. A.).

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  1. Department of Molecular and Cell Biology, Howard Hughes Medical Institute, Cancer Research Laboratory, University of California at Berkeley, Berkeley, 94720, CA, USA

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

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Correspondence to James P. Allison.

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Egen, J., Kuhns, M. & Allison, J. CTLA-4: new insights into its biological function and use in tumor immunotherapy. Nat Immunol 3, 611–618 (2002). https://doi.org/10.1038/ni0702-611

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