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A rheostat for immune responses: the unique properties of PD-1 and their advantages for clinical application

Abstract

PD-1, a negative coreceptor expressed on antigen-stimulated T cells and B cells, seems to serve as a 'rheostat' of the immune response. The molecular mechanisms of the functions of PD-1, in conjunction with the mild, chronic and strain-specific autoimmune phenotypes of PD-1-deficient mice, in contrast to the devastating fatal autoimmune disease of mice deficient in the immunomodulatory receptor CTLA-4, suggest that immunoregulation by PD-1 is rather antigen specific and is mainly cell intrinsic. Such unique properties make PD-1 a powerful target for immunological therapy, with highly effective clinical applications for cancer treatment.

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Figure 1: PD-1 induces T cell tolerance.
Figure 2: Biological importance of PD-1 signaling.
Figure 3: Distinct mechanisms of PD-1 and CTLA4 in immunosuppression.

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Acknowledgements

We thank N. Minato and colleagues at Kyoto University for scientific expertise. Supported by Core Research for Evolutional Science and Technology Program of the Japan Science and Technology Agency (T.O.), Grants-in-Aid for Scientific Research from the Japanese Ministry of Education, Culture, Sports, Science and Technology (23790534 and 25460363 to S.C.), the Senri Life Science Foundation (S.C.) and Grants-in-Aid for Scientific Research in Priority Areas and RIKEN's President Discretionary Fund (S.F.).

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Okazaki, T., Chikuma, S., Iwai, Y. et al. A rheostat for immune responses: the unique properties of PD-1 and their advantages for clinical application. Nat Immunol 14, 1212–1218 (2013). https://doi.org/10.1038/ni.2762

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