Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation.
Gordon J. Freeman,Andrew J. Long,Yoshiko Iwai,Karen Bourque,Tatyana Chernova,Hiroyuki Nishimura,Lori Fitz,Nelly Malenkovich,Taku Okazaki,Michael C. Byrne,Heidi F. Horton,Lynette A. Fouser,Laura L. Carter,Vincent Ling,Michael R Bowman,Beatriz M. Carreno,Mary Collins,Clive Wood,Tasuku Honjo +18 more
TLDR
It is reported here that the ligand of PD-1 (PD-L1), an immunoinhibitory receptor expressed by activated T cells, B cells, and myeloid cells, is a member of the B7 gene family.Abstract:
PD-1 is an immunoinhibitory receptor expressed by activated T cells, B cells, and myeloid cells. Mice deficient in PD-1 exhibit a breakdown of peripheral tolerance and demonstrate multiple autoimmune features. We report here that the ligand of PD-1 (PD-L1) is a member of the B7 gene family. Engagement of PD-1 by PD-L1 leads to the inhibition of T cell receptor-mediated lymphocyte proliferation and cytokine secretion. In addition, PD-1 signaling can inhibit at least suboptimal levels of CD28-mediated costimulation. PD-L1 is expressed by antigen-presenting cells, including human peripheral blood monocytes stimulated with interferon gamma, and activated human and murine dendritic cells. In addition, PD-L1 is expressed in nonlymphoid tissues such as heart and lung. The relative levels of inhibitory PD-L1 and costimulatory B7-1/B7-2 signals on antigen-presenting cells may determine the extent of T cell activation and consequently the threshold between tolerance and autoimmunity. PD-L1 expression on nonlymphoid tissues and its potential interaction with PD-1 may subsequently determine the extent of immune responses at sites of inflammation.read more
Citations
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Safety, activity, and immune correlates of anti-PD-1 antibody in cancer.
Suzanne L. Topalian,F. Stephen Hodi,Julie R. Brahmer,Scott N. Gettinger,David Smith,David F. McDermott,John D. Powderly,Richard D. Carvajal,Jeffrey A. Sosman,Michael B. Atkins,Philip D. Leming,David R. Spigel,Scott J. Antonia,Leora Horn,Charles G. Drake,Drew M. Pardoll,Lieping Chen,William H. Sharfman,Robert A. Anders,Janis M. Taube,Tracee L. McMiller,Haiying Xu,Alan J. Korman,Maria Jure-Kunkel,Shruti Agrawal,Dan McDonald,Georgia Kollia,Ashok Kumar Gupta,Jon M. Wigginton,Mario Sznol +29 more
TL;DR: Anti-PD-1 antibody produced objective responses in approximately one in four to one in five patients with non-small-cell lung cancer, melanoma, or renal-cell cancer; the adverse-event profile does not appear to preclude its use.
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The blockade of immune checkpoints in cancer immunotherapy
TL;DR: Preliminary clinical findings with blockers of additional immune-checkpoint proteins, such as programmed cell death protein 1 (PD1), indicate broad and diverse opportunities to enhance antitumour immunity with the potential to produce durable clinical responses.
Journal ArticleDOI
Safety and Activity of Anti–PD-L1 Antibody in Patients with Advanced Cancer
Julie R. Brahmer,Scott S. Tykodi,Scott S. Tykodi,Laura Q.M. Chow,Wen-Jen Hwu,Suzanne L. Topalian,Patrick Hwu,Charles G. Drake,Luis H. Camacho,John S. Kauh,Kunle Odunsi,Henry C. Pitot,Omid Hamid,Shailender Bhatia,Renato G. Martins,Keith D. Eaton,Shuming Chen,Theresa M. Salay,Suresh Alaparthy,Joseph F. Grosso,Alan J. Korman,Susan M. Parker,Shruti Agrawal,Stacie M. Goldberg,Drew M. Pardoll,Ashok Kumar Gupta,Jon M. Wigginton +26 more
TL;DR: Antibody-mediated blockade of PD-L1 induced durable tumor regression and prolonged stabilization of disease in patients with advanced cancers, including non-small-cell lung cancer, melanoma, and renal-cell cancer.
Journal ArticleDOI
Pembrolizumab for the treatment of non-small cell lung cancer
Edward B. Garon,Naiyer A. Rizvi,Rina Hui,Natasha B. Leighl,Ani Sarkis Balmanoukian,Joseph Paul Eder,Amita Patnaik,Charu Aggarwal,Matthew A. Gubens,Leora Horn,Enric Carcereny,Myung-Ju Ahn,Enriqueta Felip,Jong-Seok Lee,Matthew D. Hellmann,Omid Hamid,Jonathan W. Goldman,Jean-Charles Soria,Marisa Dolled-Filhart,Ruth Z. Rutledge,Jin Zhang,Jared Lunceford,Reshma A. Rangwala,Gregory M. Lubiniecki,Charlotte Roach,Kenneth Emancipator,Leena Gandhi +26 more
TL;DR: Pembrolizumab had an acceptable side-effect profile and showed antitumor activity in patients with advanced non-small-cell lung cancer and PD-L1 expression in at least 50% of tumor cells correlated with improved efficacy of pembrolIZumab.
Journal ArticleDOI
Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled trial.
Roy S. Herbst,Paul Baas,Dong Wan Kim,Enriqueta Felip,Jose Luis Perez-Gracia,Ji Youn Han,Julian R. Molina,Joo Hang Kim,Catherine Dubos Arvis,Myung-Ju Ahn,Margarita Majem,Mary J. Fidler,Gilberto de Castro,Marcelo Garrido,Gregory M. Lubiniecki,Yue Shentu,Ellie Im,Marisa Dolled-Filhart,Edward B. Garon +18 more
TL;DR: In this article, the authors evaluated the efficacy of pembrolizumab for patients with previously treated, PD-L1-positive, advanced non-small-cell lung cancer.
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