Journal ArticleDOI
The future of immune checkpoint therapy
Padmanee Sharma,James P. Allison +1 more
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TLDR
The way forward for this class of novel agents lies in the ability to understand human immune responses in the tumor microenvironment, which will provide valuable information regarding the dynamic nature of the immune response and regulation of additional pathways that will need to be targeted through combination therapies to provide survival benefit for greater numbers of patients.Abstract:
Immune checkpoint therapy, which targets regulatory pathways in T cells to enhance antitumor immune responses, has led to important clinical advances and provided a new weapon against cancer. This therapy has elicited durable clinical responses and, in a fraction of patients, long-term remissions where patients exhibit no clinical signs of cancer for many years. The way forward for this class of novel agents lies in our ability to understand human immune responses in the tumor microenvironment. This will provide valuable information regarding the dynamic nature of the immune response and regulation of additional pathways that will need to be targeted through combination therapies to provide survival benefit for greater numbers of patients.read more
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Journal ArticleDOI
Developing Covalent Protein Drugs via Proximity-Enabled Reactive Therapeutics.
Qingke Li,Qu Chen,Paul C. Klauser,Mengyuan Li,Mengyuan Li,Feng Zheng,Nanxi Wang,Xiaoying Li,Qianbing Zhang,Xuemei Fu,Qian Wang,Yang Xu,Yang Xu,Lei Wang +13 more
TL;DR: A proximity-enabled reactive therapeutics (PERx) approach to generate covalent protein drugs that exhibited strikingly more potent antitumor effect over the noncovalent wild-type PD-1, attaining therapeutic efficacy equivalent or superior to anti-PD-L1 antibody.
Journal ArticleDOI
Notch Shapes the Innate Immunophenotype in Breast Cancer.
Qiang Shen,Brenda Cohen,Weiyue Zheng,Ramtin Rahbar,Bernard Martin,Kiichi Murakami,Sara Lamorte,Patrycja K. Thompson,Hal K. Berman,Hal K. Berman,Juan Carlos Zúñiga-Pflücker,Pamela S. Ohashi,Pamela S. Ohashi,Michael Reedijk,Michael Reedijk,Michael Reedijk +15 more
TL;DR: Notch in tumor cells regulates the expression of two powerful proinflammatory cytokines, IL1β and CCL2, and the recruitment of tumor-associated macrophages (TAM), closing a Notch-dependent paracrine signaling loop between these two cell types.
Posted ContentDOI
Collagen density regulates the activity of tumor-infiltrating T cells
Dorota Ewa Kuczek,Anne Mette Hvid Larsen,Anne Mette Hvid Larsen,Marco Carretta,Adrija Kalvisa,Majken S. Siersbæk,Ana Micaela Carnaz Simoes,Anne Roslind,Lars H. Engelholm,Marco Donia,Inge Marie Svane,Per thor Straten,Per thor Straten,Lars Grøntved,Daniel H. Madsen +14 more
TL;DR: A reduction in the number of infiltrating CD8+ T-cells in mammary tumors with high collagen- density is observed indicating that collagen-density has a role in regulating T cell abundance in human breast cancer.
Journal ArticleDOI
The Course of Immune Stimulation by Photodynamic Therapy: Bridging Fundamentals of Photochemically Induced Immunogenic Cell Death to the Enrichment of T-Cell Repertoire.
TL;DR: A hypothesis is postulate that during the course of the immune stimulation process, PDT also enriches the T‐cell repertoire with tumor‐reactive activated T cells, diversifying their tumor‐specific targets and eliciting a more expansive and rigorous antitumor response.
Journal ArticleDOI
Trained Immunity-Promoting Nanobiologic Therapy Suppresses Tumor Growth and Potentiates Checkpoint Inhibition.
Bram Priem,Mandy M. T. van Leent,Mandy M. T. van Leent,Abraham J. P. Teunissen,Alexandros Marios Sofias,Alexandros Marios Sofias,Vera P. Mourits,Lisa Willemsen,Emma D. Klein,Roderick S. Oosterwijk,Anu E. Meerwaldt,Anu E. Meerwaldt,Jazz Munitz,Geoffrey Prévot,Anna Vera D Verschuur,Sheqouia A. Nauta,Esther M. van Leeuwen,Elizabeth L. Fisher,Karen A.M. de Jong,Yiming Zhao,Yohana C. Toner,Georgios Soultanidis,Claudia Calcagno,Paul H. H. Bomans,Heiner Friedrich,Nico A. J. M. Sommerdijk,Thomas Reiner,Thomas Reiner,Raphaël Duivenvoorden,Raphaël Duivenvoorden,Eva Zupančič,Julie Di Martino,Ewelina Kluza,Mohammad Rashidian,Hidde L. Ploegh,Rick M. Dijkhuizen,Sjoerd Hak,Carlos Pérez-Medina,Carlos Pérez-Medina,Jose Javier Bravo-Cordero,Menno P.J. de Winther,Leo A. B. Joosten,Leo A. B. Joosten,Andrea van Elsas,Zahi A. Fayad,Alexander Rialdi,Denis Torre,Ernesto Guccione,Jordi Ochando,Jordi Ochando,Mihai G. Netea,Mihai G. Netea,Mihai G. Netea,Arjan W. Griffioen,Willem J. M. Mulder +54 more
TL;DR: It is shown that rationally designed nanobiologics can promote trained immunity and elicit a durable anti-tumor response either as a monotherapy or in combination with checkpoint inhibitor drugs.
References
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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
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Safety, activity, and immune correlates of anti-PD-1 antibody in cancer.
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The blockade of immune checkpoints in cancer immunotherapy
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Mutations of the BRAF gene in human cancer
Helen Davies,Graham R. Bignell,Charles Cox,Philip J. Stephens,Sarah Edkins,S. M. Clegg,Jon W. Teague,Hayley Woffendin,Mathew J. Garnett,William Bottomley,Neil Davis,Ed Dicks,Rebecca Ewing,Yvonne Floyd,Kristian Gray,S. Hall,Rachel Hawes,Jaime Hughes,Vivian Kosmidou,Andrew Menzies,Catherine Mould,Adrian Parker,Claire Stevens,Stephen Watt,Steven Hooper,Rebecca Wilson,Hiran Jayatilake,Barry A. Gusterson,Colin Cooper,Janet Shipley,Darren Hargrave,Kathy Pritchard-Jones,Norman J. Maitland,Georgia Chenevix-Trench,Gregory J. Riggins,Darell D. Bigner,Giuseppe Palmieri,Antonio Cossu,Adrienne M. Flanagan,Andrew G. Nicholson,Judy W. C. Ho,Suet Yi Leung,Siu Tsan Yuen,Barbara L. Weber,Hilliard F. Seigler,Timothy L. Darrow,Hugh Paterson,Richard Marais,Christopher J. Marshall,Richard Wooster,Michael R. Stratton,P. Andrew Futreal +51 more
TL;DR: BRAF somatic missense mutations in 66% of malignant melanomas and at lower frequency in a wide range of human cancers, with a single substitution (V599E) accounting for 80%.
Journal ArticleDOI
Signatures of mutational processes in human cancer
Ludmil B. Alexandrov,Serena Nik-Zainal,Serena Nik-Zainal,David C. Wedge,Samuel Aparicio,Sam Behjati,Sam Behjati,Andrew V. Biankin,Graham R. Bignell,Niccolo Bolli,Niccolo Bolli,Åke Borg,Anne Lise Børresen-Dale,Anne Lise Børresen-Dale,Sandrine Boyault,Birgit Burkhardt,Adam Butler,Carlos Caldas,Helen Davies,Christine Desmedt,Roland Eils,Jorunn E. Eyfjord,John A. Foekens,Mel Greaves,Fumie Hosoda,Barbara Hutter,Tomislav Ilicic,Sandrine Imbeaud,Sandrine Imbeaud,Marcin Imielinsk,Natalie Jäger,David T. W. Jones,David T. Jones,Stian Knappskog,Stian Knappskog,Marcel Kool,Sunil R. Lakhani,Carlos López-Otín,Sancha Martin,Nikhil C. Munshi,Nikhil C. Munshi,Hiromi Nakamura,Paul A. Northcott,Marina Pajic,Elli Papaemmanuil,Angelo Paradiso,John V. Pearson,Xose S. Puente,Keiran Raine,Manasa Ramakrishna,Andrea L. Richardson,Andrea L. Richardson,Julia Richter,Philip Rosenstiel,Matthias Schlesner,Ton N. Schumacher,Paul N. Span,Jon W. Teague,Yasushi Totoki,Andrew Tutt,Rafael Valdés-Mas,Marit M. van Buuren,Laura van ’t Veer,Anne Vincent-Salomon,Nicola Waddell,Lucy R. Yates,Icgc PedBrain,Jessica Zucman-Rossi,Jessica Zucman-Rossi,P. Andrew Futreal,Ultan McDermott,Peter Lichter,Matthew Meyerson,Matthew Meyerson,Sean M. Grimmond,Reiner Siebert,Elias Campo,Tatsuhiro Shibata,Stefan M. Pfister,Stefan M. Pfister,Peter J. Campbell,Peter J. Campbell,Peter J. Campbell,Michael R. Stratton,Michael R. Stratton +84 more
TL;DR: It is shown that hypermutation localized to small genomic regions, ‘kataegis’, is found in many cancer types, and this results reveal the diversity of mutational processes underlying the development of cancer.
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