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

被引:765
作者
Okazaki, Taku [1 ]
Chikuma, Shunsuke [2 ]
Iwai, Yoshiko [3 ]
Fagarasan, Sidonia [4 ]
Honjo, Tasuku [2 ]
机构
[1] Univ Tokushima, Inst Genome Res, Div Immune Regulat, Tokushima 770, Japan
[2] Kyoto Univ, Grad Sch Med, Dept Immunol & Genom Med, Kyoto, Japan
[3] Univ Occupat & Environm Hlth, Sch Med, Dept Mol Biol, Kitakyushu, Fukuoka 807, Japan
[4] RIKEN Yokohama Inst, Ctr Integrat Med Sci IMS RCAI, Lab Mucosal Immun, Yokohama, Kanagawa, Japan
基金
日本科学技术振兴机构;
关键词
T-CELLS; REGULATORY T; DILATED CARDIOMYOPATHY; PROGRAMMED DEATH-1; TUMOR-IMMUNOTHERAPY; NEGATIVE REGULATOR; CRYSTAL-STRUCTURE; EFFECTOR PHASE; CUTTING EDGE; TGF-BETA;
D O I
10.1038/ni.2762
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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.
引用
收藏
页码:1212 / 1218
页数:7
相关论文
共 90 条
[1]   Expression of the PD-1 antigen on the surface of stimulated mouse T and B lymphocytes [J].
Agata, Y ;
Kawasaki, A ;
Nishimura, H ;
Ishida, Y ;
Tsubata, T ;
Yagita, H ;
Honjo, T .
INTERNATIONAL IMMUNOLOGY, 1996, 8 (05) :765-772
[2]  
Bachmann MF, 1999, J IMMUNOL, V163, P1128
[3]   Restoring function in exhausted CD8 T cells during chronic viral infection [J].
Barber, DL ;
Wherry, EJ ;
Masopust, D ;
Zhu, BG ;
Allison, JP ;
Sharpe, AH ;
Freeman, GJ ;
Ahmed, R .
NATURE, 2006, 439 (7077) :682-687
[4]   PD-L1/B7H-1 inhibits the effector phase of tumor rejection by T cell receptor (TCR) transgenic CD8+ T cells [J].
Blank, C ;
Brown, I ;
Peterson, AC ;
Spiotto, M ;
Iwai, Y ;
Honjo, T ;
Gajewski, TF .
CANCER RESEARCH, 2004, 64 (03) :1140-1145
[5]   Intrinsic and extrinsic control of peripheral T-cell tolerance by costimulatory molecules of the CD28/B7 family [J].
Bour-Jordan, Helene ;
Esensten, Jonathan H. ;
Martinez-Llordella, Marc ;
Penaranda, Cristina ;
Stumpf, Melanie ;
Bluestone, Jeffrey A. .
IMMUNOLOGICAL REVIEWS, 2011, 241 :180-205
[6]   Safety and Activity of Anti-PD-L1 Antibody in Patients with Advanced Cancer [J].
Brahmer, Julie R. ;
Tykodi, Scott S. ;
Chow, Laura Q. M. ;
Hwu, Wen-Jen ;
Topalian, Suzanne L. ;
Hwu, Patrick ;
Drake, Charles G. ;
Camacho, Luis H. ;
Kauh, John ;
Odunsi, Kunle ;
Pitot, Henry C. ;
Hamid, Omid ;
Bhatia, Shailender ;
Martins, Renato ;
Eaton, Keith ;
Chen, Shuming ;
Salay, Theresa M. ;
Alaparthy, Suresh ;
Grosso, Joseph F. ;
Korman, Alan J. ;
Parker, Susan M. ;
Agrawal, Shruti ;
Goldberg, Stacie M. ;
Pardoll, Drew M. ;
Gupta, Ashok ;
Wigginton, Jon M. .
NEW ENGLAND JOURNAL OF MEDICINE, 2012, 366 (26) :2455-2465
[7]   Phase I Study of Single-Agent Anti-Programmed Death-1 (MDX-1106) in Refractory Solid Tumors: Safety, Clinical Activity, Pharmacodynamics, and Immunologic Correlates [J].
Brahmer, Julie R. ;
Drake, Charles G. ;
Wollner, Ira ;
Powderly, John D. ;
Picus, Joel ;
Sharfman, William H. ;
Stankevich, Elizabeth ;
Pons, Alice ;
Salay, Theresa M. ;
McMiller, Tracee L. ;
Gilson, Marta M. ;
Wang, Changyu ;
Selby, Mark ;
Taube, Janis M. ;
Anders, Robert ;
Chen, Lieping ;
Korman, Alan J. ;
Pardoll, Drew M. ;
Lowy, Israel ;
Topalian, Suzanne L. .
JOURNAL OF CLINICAL ONCOLOGY, 2010, 28 (19) :3167-3175
[8]   SHP-1 and SHP-2 associate with immunoreceptor tyrosine-based switch motif of programmed death 1 upon primary human T cell stimulation, but only receptor ligation prevents T cell activation [J].
Chemnitz, JM ;
Parry, RV ;
Nichols, KE ;
June, CH ;
Riley, JL .
JOURNAL OF IMMUNOLOGY, 2004, 173 (02) :945-954
[9]   PD-1-Mediated Suppression of IL-2 Production Induces CD8+ T Cell Anergy In Vivo [J].
Chikuma, Shunsuke ;
Terawaki, Seigo ;
Hayashi, Tamon ;
Nabeshima, Ryusuke ;
Yoshida, Takao ;
Shibayama, Shiro ;
Okazaki, Taku ;
Honjo, Tasuku .
JOURNAL OF IMMUNOLOGY, 2009, 182 (11) :6682-6689
[10]   Follicular regulatory T cells expressing Foxp3 and Bcl-6 suppress germinal center reactions [J].
Chung, Yeonseok ;
Tanaka, Shinya ;
Chu, Fuliang ;
Nurieva, Roza I. ;
Martinez, Gustavo J. ;
Rawal, Seema ;
Wang, Yi-Hong ;
Lim, Hoyong ;
Reynolds, Joseph M. ;
Zhou, Xiao-hui ;
Fan, Hui-min ;
Liu, Zhong-ming ;
Neelapu, Sattva S. ;
Dong, Chen .
NATURE MEDICINE, 2011, 17 (08) :983-U102