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

Taku Okazaki, Shunsuke Chikuma, Yoshiko Iwai, Sidonia Fagarasan, Tasuku Honjo, Taku Okazaki, Shunsuke Chikuma, Yoshiko Iwai, Sidonia Fagarasan, Tasuku Honjo

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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