Journal ArticleDOI
Immune checkpoints and their inhibition in cancer and infectious diseases.
Lydia Dyck,Kingston H. G. Mills +1 more
TLDR
These inhibitors have great potential for treating chronic infections, especially when combined with therapeutic vaccines, and have been shown to enhance ex vivo effector T‐cell responses from patients with chronic viral, bacterial, or parasitic infection.Abstract:
The development of chronic infections and cancer is facilitated by a variety of immune subversion mechanisms, such as the production of anti-inflammatory cytokines, induction of regulatory T (Treg) cells, and expression of immune checkpoint molecules, including CTLA-4 and PD-1. CTLA-4, expressed on T cells, interacts with CD80/CD86, thereby limiting T-cell activation and leading to anergy. PD-1 is predominantly expressed on T cells and its interaction with PD-L1 and PD-L2 expressed on antigen-presenting cells (APCs) and tumors sends a negative signal to T cells, which can lead to T-cell exhaustion. Given their role in suppressing effector T-cell responses, immune checkpoints are being targeted for the treatment of cancer. Indeed, antibodies binding to CTLA-4, PD-1, or PD-L1 have shown remarkable efficacy, especially in combination therapies, for a number of cancers and have been licensed for the treatment of melanoma, nonsmall cell lung cancer, and renal and bladder cancers. Moreover, immune checkpoint inhibitors have been shown to enhance ex vivo effector T-cell responses from patients with chronic viral, bacterial, or parasitic infection, including HIV, tuberculosis, and malaria. Although the data from clinical trials in infectious diseases are still sparse, these inhibitors have great potential for treating chronic infections, especially when combined with therapeutic vaccines.read more
Citations
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Immune Checkpoints in Leprosy: Immunotherapy As a Feasible Approach to Control Disease Progression.
Hayana Ramos Lima,Thaís Helena Gasparoto,Tatiana Salles de Souza Malaspina,Vinicius Rizzo Marques,Marina Jurado Vicente,Elaine Camarinha Marcos,Fabiana Corvolo Souza,Maria Renata Sales Nogueira,Jaison Antônio Barreto,Gustavo Pompermaier Garlet,João Santana da Silva,Vânia Nieto Brito-de-Souza,Ana Paula Campanelli +12 more
TL;DR: How the co-inhibitory molecules PD-1, PD-L1, and Th1/Th17 versus Th2/Treg cells are balanced, how antigen-presenting cell maturation acts at different levels to inhibit T cells and modulate the development of leprosy, and how new interventions interfere with leproSy development are outlined.
Journal ArticleDOI
Checkpoints and Immunity in Cancers: Role of GNG12.
Abdullahi Alausa,Ugwu Chukwuebuka Victor,Olumide Samuel Fadahunsi,Nurudeen O. Owolabi,Adeolu Adeniji,Mercy Olatinwo,Abdeen Tunde Ogunlana,Barakat Olaleke,Toheeb A. Balogun,Sunday Ogundepo,Peter Ifeoluwa Adegboola +10 more
TL;DR: In this paper , the authors established the silent role of GNG12 in activating NF-kB genes and the synergism between NF-B and PD-L1 expression, and reported that silencing GNN12 gene downregulates the transcription of PD-l1 gene.
Journal ArticleDOI
Similar Clinical Course and Significance of Circulating Innate and Adaptive Immune Cell Counts in STEMI and COVID-19.
Elena de Dios,Cesar Rios-Navarro,Nerea Perez-Sole,Jose Gavara,Víctor Marcos-Garcés,Enrique Rodríguez,Arturo Carratalá,María José Forner,Jorge A. R. Navarro,Maria L. Blasco,Elvira Bondia,Jaime Signes-Costa,José M. Vila,Maria J. Forteza,Francisco J. Chorro,Vicente Bodi +15 more
TL;DR: Time course of circulating neutrophil and lymphocyte counts and their ratio (NLR) in ST-segment elevation myocardial infarction (STEMI) and coronavirus disease (COVID)-19 is assessed to explore their associations with clinical events and structural damage.
Journal ArticleDOI
Identification of SCN7A as the key gene associated with tumor mutation burden in gastric cancer
TL;DR: Wang et al. as discussed by the authors used weighted gene coexpression network analysis (WGCNA) algorithm to cluster the most relevant TMB modules in the Cancer Genome Atlas (TCGA) database.
Journal ArticleDOI
Managing viral hepatitis in cancer patients under immune checkpoint inhibitors: should we take the risk?
Stijn J De Keukeleire,Tijl Vermassen,Zahra M Nezhad,Tessa Kerre,Vibeke Kruse,Hans Van Vlierberghe,Karim Vermaelen,Sylvie Rottey +7 more
TL;DR: In this paper, the safety and efficacy of immune checkpoint inhibitors (ICIs) in patients with chronic hepatitis B and C infection were investigated, and the authors identified eight studies of cancer patients with viral hepatitis treated with one or more ICIs, formally assessed tumor responses and safety by grading liver dysfunction.
References
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Journal ArticleDOI
Improved Survival with Ipilimumab in Patients with Metastatic Melanoma.
F. Stephen Hodi,Steven J. O'Day,David F. McDermott,R. W. Weber,Jeffrey A. Sosman,John B. A. G. Haanen,Rene Gonzalez,Caroline Robert,Dirk Schadendorf,Jessica C. Hassel,Wallace Akerley,Alfons J.M. van den Eertwegh,Jose Lutzky,Paul Lorigan,Julia Vaubel,Gerald P. Linette,David W. Hogg,Christian H. Ottensmeier,Céleste Lebbé,Christian Peschel,Ian Quirt,Joseph I. Clark,Jedd D. Wolchok,Jeffrey S. Weber,Jason Tian,Michael Yellin,Geoffrey M. Nichol,Axel Hoos,Walter J. Urba +28 more
TL;DR: Ipilimumab, with or without a gp100 peptide vaccine, as compared with gp100 alone, improved overall survival in patients with previously treated metastatic melanoma.
Journal ArticleDOI
Combined Nivolumab and Ipilimumab or Monotherapy in Untreated Melanoma.
James Larkin,Vanna Chiarion-Sileni,Rene Gonzalez,Jean-Jacques Grob,C. Lance Cowey,Christopher D. Lao,Dirk Schadendorf,Reinhard Dummer,Michael Smylie,Piotr Rutkowski,Pier Francesco Ferrucci,A. Hill,John Wagstaff,Matteo S. Carlino,John B A G Haanen,Michele Maio,Ivan Marquez-Rodas,Grant A. McArthur,Paolo A. Ascierto,Georgina V. Long,Margaret K. Callahan,Michael A. Postow,Michael A. Postow,Kenneth F. Grossmann,Mario Sznol,Brigitte Dréno,Lars Bastholt,Arvin Yang,Linda Rollin,Christine Horak,F. Stephen Hodi,Jedd D. Wolchok,Jedd D. Wolchok +32 more
TL;DR: Among previously untreated patients with metastatic melanoma, nivolumab alone or combined with ipilimumab resulted in significantly longer progression-free survival than ipILimumab alone, and in patients with PD-L1-negative tumors, the combination of PD-1 and CTLA-4 blockade was more effective than either agent alone.
Journal ArticleDOI
Type, Density, and Location of Immune Cells Within Human Colorectal Tumors Predict Clinical Outcome
Jérôme Galon,Anne Costes,Fátima Sánchez-Cabo,Amos Kirilovsky,Bernhard Mlecnik,Christine Lagorce-Pagès,Marie Tosolini,Matthieu Camus,Anne Berger,Philippe Wind,Franck Zinzindohoué,Patrick Bruneval,Paul-Henri Cugnenc,Zlatko Trajanoski,Wolf H. Fridman,Franck Pagès +15 more
TL;DR: In situ analysis of tumor-infiltrating immune cells may be a valuable prognostic tool in the treatment of colorectal cancer and possibly other malignancies.
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
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.
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Improved Survival with Ipilimumab in Patients with Metastatic Melanoma.
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Combined Nivolumab and Ipilimumab or Monotherapy in Untreated Melanoma.
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