Expression of Programmed Death 1 Ligands by Murine T Cells and APC
Tomohide Yamazaki,Hisaya Akiba,Hideyuki Iwai,Hironori Matsuda,Mami Aoki,Yuka Tanno,Tahiro Shin,Haruo Tsuchiya,Drew M. Pardoll,Ko Okumura,Miyuki Azuma,Hideo Yagita +11 more
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TLDR
B7-H1 was broadly expressed on the surface of mouse tumor cell lines while the expression of B7-DC was rather restricted, and the inducible expression of PD-1 ligands on both T cells and APCs may suggest new paradigms ofPD-1-mediated immune regulation.Abstract:
Programmed death 1 (PD-1) is a new member of the CD28/CTLA-4 family, which has been implicated in the maintenance of peripheral tolerance. Two ligands for PD-1, namely, B7-H1 (PD-L1) and B7-DC (PD-L2), have recently been identified as new members of the B7 family but their expression at the protein level remains largely unknown. To characterize the expression of B7-H1 and B7-DC, we newly generated an anti-mouse B7-H1 mAb (MIH6) and an anti-mouse B7-DC mAb (TY25). MIH6 and TY25 immunoprecipitated a single molecule of 43 and 42 kDa from the lysate of B7-H1 and B7-DC transfectants, respectively. Flow cytometric analysis revealed that B7-H1 was broadly expressed on the surface of mouse tumor cell lines while the expression of B7-DC was rather restricted. PD-1 was expressed on anti-CD3-stimulated T cells and anti-IgM plus anti-CD40-stimulated B cells at high levels but was undetectable on activated macrophages or DCs. B7-H1 was constitutively expressed on freshly isolated splenic T cells, B cells, macrophages, and dendritic cells (DCs), and up-regulated on T cells by anti-CD3 stimulation on macrophages by LPS, IFN-gamma, GM-CSF, or IL-4, and on DCs by IFN-gamma, GM-CSF, or IL-4. In contrast, B7-DC expression was only inducible on macrophages and DCs upon stimulation with IFN-gamma, GM-CSF, or IL-4. The inducible expression of PD-1 ligands on both T cells and APCs may suggest new paradigms of PD-1-mediated immune regulation.read more
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PD-1 and its ligands in tolerance and immunity
TL;DR: Current understanding of the immunoregulatory functions of PD-1 and its ligands and their therapeutic potential are discussed and an inhibitory bidirectional interaction between PD-L1 and B7-1 is discovered, revealing new ways the B7:CD28 family regulates T cell activation and tolerance.
Journal ArticleDOI
Association of PD-1, PD-1 ligands, and other features of the tumor immune microenvironment with response to anti-PD-1 therapy
Janis M. Taube,Alison P. Klein,Julie R. Brahmer,Haiying Xu,Xiaoyu Pan,Jung H. Kim,Lieping Chen,Drew M. Pardoll,Suzanne L. Topalian,Robert A. Anders +9 more
TL;DR: Tumor PD-L1 expression reflects an immune-active microenvironment and, while associated other immunosuppressive molecules, including PD-1 andPD-L2, is the single factor most closely correlated with response to anti–PD-1 blockade.
Journal ArticleDOI
Colocalization of Inflammatory Response with B7-H1 Expression in Human Melanocytic Lesions Supports an Adaptive Resistance Mechanism of Immune Escape
Janis M. Taube,Robert A. Anders,Geoffrey D. Young,Haiying Xu,Rajni Sharma,Tracee L. McMiller,Shuming Chen,Alison P. Klein,Drew M. Pardoll,Suzanne L. Topalian,Lieping Chen,Lieping Chen +11 more
TL;DR: Induction of the B7-H1/PD-1 pathway may represent an adaptive immune resistance mechanism exerted by tumor cells in response to endogenous antitumor activity and may explain how melanomas escape immune destruction despite endogenous antitUMor immune responses.
Journal ArticleDOI
Co-inhibitory molecules of the B7-CD28 family in the control of T-cell immunity.
TL;DR: Several newly described co-inhibitory pathways in the B7–CD28 family are focused on, which control the priming, growth, differentiation and functional maturation of a T-cell response.
Journal ArticleDOI
PD-1 and PD-1 ligands: from discovery to clinical application.
Taku Okazaki,Tasuku Honjo +1 more
TL;DR: The history ofPD-1 research since its discovery and recent findings that suggest promising future for the clinical application of PD-1 agonists and antagonists to various human diseases are summarized.
References
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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
TL;DR: 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.
Journal ArticleDOI
Tumor-associated B7-H1 promotes T-cell apoptosis: a potential mechanism of immune evasion
Haidong Dong,Scott E. Strome,Diva R. Salomao,Hideto Tamura,Fumiya Hirano,Dallas B. Flies,Patrick C. Roche,Jun Lu,Gefeng Zhu,Koji Tamada,Vanda A. Lennon,Esteban Celis,Lieping Chen +12 more
TL;DR: It is reported here that, except for cells of the macrophage lineage, normal human tissues do not express B7-H1 and the findings have implications for the design of T cell–based cancer immunotherapy.
Journal ArticleDOI
PD-L2 is a second ligand for PD-1 and inhibits T cell activation
Yvette Latchman,Clive Wood,Tatyana Chernova,Divya Chaudhary,Madhuri Borde,Irene Chernova,Yoshiko Iwai,Andrew J. Long,Julia A. Brown,Raquel A. Nunes,Edward A. Greenfield,Karen Bourque,Vassiliki A. Boussiotis,Laura L. Carter,Beatriz M. Carreno,Nelly Malenkovich,Hiroyuki Nishimura,Taku Okazaki,Tasuku Honjo,Arlene H. Sharpe,Gordon J. Freeman +20 more
TL;DR: These studies show overlapping functions of PD-L1 andPD-L2 and indicate a key role for the PD- L–PD-1 pathway in regulating T cell responses.
Journal ArticleDOI
Induced expression of PD-1, a novel member of the immunoglobulin gene superfamily, upon programmed cell death.
TL;DR: The results suggest that activation of the PD‐1 gene may be involved in the classical type of programmed cell death.
Journal ArticleDOI
Development of lupus-like autoimmune diseases by disruption of the PD-1 gene encoding an ITIM motif-carrying immunoreceptor.
TL;DR: It is suggested that PD-1 is involved in the maintenance of peripheral self-tolerance by serving as a negative regulator of immune responses in lymphocytes and monocytic cells following activation.
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