A snapshot of the PD-1/PD-L1 pathway.
Chinmoy Ghosh,Gary Luong,Yue Sun +2 more
TLDR
In this paper, the authors provide a snapshot of the PD-1/PD-L1 molecular structure, mechanisms controlling their expression, signaling modulated by PD, 1/PDL1, current anti-PD-1 and 2/L1 therapies, and the future perspectives to overcome the resistance.Abstract:
Cancer cells can evade the attack from host immune systems via hijacking the regulatory circuits mediated by immune checkpoints. Therefore, reactivating the antitumor immunity by blockade of immune checkpoints is considered as a promising strategy to treat cancer. Programmed death protein 1 (PD-1) and its ligand programmed death-ligand 1 (PD-L1) are critical immune checkpoint proteins that responsible for negative regulation of the stability and the integrity of T-cell immune function. Anti-PD-1/PD-L1 drugs have been developed for immune checkpoint blockade and can induce clinical responses across different types of cancers, which provides a new hope to cure cancer. However, the patients' response rates to current anti-PD-1 or anti-PD-L1 therapies are still low and many initial responders finally develop resistance to these therapies. In this review, we provides a snapshot of the PD-1/PD-L1 molecular structure, mechanisms controlling their expression, signaling modulated by PD-1/PD-L1, current anti-PD-1/PD-L1 therapies, and the future perspectives to overcome the resistance.read more
Citations
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Improvement of the anticancer efficacy of PD-1/PD-L1 blockade via combination therapy and PD-L1 regulation
TL;DR: In this article , the PD-1/PD-L1 pathway inhibits the anticancer effect of T cells in the tumor microenvironment (TME), which in turn regulates the expression levels of PD1 and PDL1 through multiple mechanisms.
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Soluble Programmed Death Ligand-1 (sPD-L1): A Pool of Circulating Proteins Implicated in Health and Diseases.
TL;DR: In this article, the authors reviewed the different origins and roles of sPD-L1 in humans to highlight the biochemical and functional heterogeneity of the soluble protein, and the structural heterogeneity of s PD-L 1 proteins should be kept in mind when considering sPDL1 as a biomarker or as a drug target.
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The Effect of the Gut Microbiota on Systemic and Anti-Tumor Immunity and Response to Systemic Therapy against Cancer
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Glucocorticoid and pd-1 cross-talk: Does the immune system become confused?
TL;DR: In this paper, the authors examined GC signaling and how it intersects with PD-1/PD-L1 pathways, including a discussion on the potential for GC- and PD- 1/PD L1-targeted therapies to "confuse" the immune system, leading to a cancer cell advantage that counteracts anti-cancer immunotherapy.
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Fat mass and obesity‐associated protein regulates arecoline‐exposed oral cancer immune response through programmed cell death‐ligand 1
TL;DR: It is revealed that chronic arecoline exposure substantially induces upregulation of fat mass and obesity‐associated protein (FTO), MYC, and programmed cell death‐ligand 1 (PD‐L1) in OSCC cells, and it is demonstrated that are coline‐induced FTO promotes the stability and expression levels of PD‐L 1 transcripts through mediating m6A modification and MYC activity, respectively.
References
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Journal ArticleDOI
Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012.
Jacques Ferlay,Isabelle Soerjomataram,Rajesh Dikshit,Sultan Eser,Colin Mathers,Marise Souto Rebelo,Donald Maxwell Parkin,David Forman,Freddie Bray +8 more
TL;DR: The GLOBOCAN series of the International Agency for Research on Cancer (IARC) as mentioned in this paper provides estimates of the worldwide incidence and mortality from 27 major cancers and for all cancers combined for 2012.
Journal ArticleDOI
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.
Journal ArticleDOI
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
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
Pembrolizumab versus Ipilimumab in Advanced Melanoma
Caroline Robert,Caroline Robert,Caroline Robert,Jacob Schachter,Georgina V. Long,Ana Arance,Jean-Jacques Grob,Laurent Mortier,Laurent Mortier,Adil Daud,Matteo S. Carlino,Catriona M. McNeil,Michal Lotem,James Larkin,Paul Lorigan,Bart Neyns,Christian U. Blank,Omid Hamid,Christine Mateus,Christine Mateus,Ronnie Shapira-Frommer,Ronnie Shapira-Frommer,Michele Kosh,Honghong Zhou,Nageatte Ibrahim,Scot Ebbinghaus,Antoni Ribas +26 more
TL;DR: The anti-PD-1 antibody pembrolizumab prolonged progression-free survival and overall survival and had less high-grade toxicity than did ipilimumab in patients with advanced melanoma.