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
Citations
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Blocking IFNAR1 inhibits multiple myeloma-driven Treg expansion and immunosuppression.
Yawara Kawano,Yawara Kawano,Oksana Zavidij,Jihye Park,Michele Moschetta,Katsutoshi Kokubun,Tarek H. Mouhieddine,Salomon Manier,Yuji Mishima,Naoka Murakami,Mark Bustoros,Romanos Sklavenitis Pistofidis,Mairead Reidy,Yu J. Shen,Mahshid Rahmat,Pavlo Lukyanchykov,Esilida Sula Karreci,Shokichi Tsukamoto,Jiantao Shi,Satoshi Takagi,Daisy Huynh,Antonio Sacco,Antonio Sacco,Yu-Tzu Tai,Marta Chesi,P. Leif Bergsagel,Aldo M. Roccaro,Aldo M. Roccaro,Jamil Azzi,Irene M. Ghobrial +29 more
TL;DR: It is demonstrated that myeloma cells drive Treg expansion and activation by secreting type 1 interferon (IFN), and blocking type 1 IFN signaling represents a potential strategy to target immunosuppressive Treg function in MM.
Journal ArticleDOI
Evolutionary dynamics of neoantigens in growing tumors.
Eszter Lakatos,Marc J Williams,Ryan O. Schenck,William Cross,Jacob Househam,Luis Zapata,Benjamin Werner,Benjamin Werner,Chandler Gatenbee,Mark Robertson-Tessi,Chris P. Barnes,Alexander R. A. Anderson,Andrea Sottoriva,Trevor A. Graham +13 more
TL;DR: M Mathematical modeling of evolutionary dynamics of neoantigens and immune escape in growing tumors shows that strong negative selection for neoantIGens inhibits tumor growth but also provides a strong selective pressure for the evolution of immune escape.
Journal ArticleDOI
Regulation of Astrocyte Functions in Multiple Sclerosis.
TL;DR: Positive and negative regulators of astrocyte-mediated pathogenesis in MS, such as sphingolipid metabolism and aryl hydrocarbon receptor signaling, are described.
Journal ArticleDOI
Tissue-Specific Immunoregulation: A Call for Better Understanding of the “Immunostat” in the Context of Cancer
W. Pao,Chia Huey Ooi,Fabian Birzele,Astrid Ruefli-Brasse,Michael A. Cannarile,Bernhard Reis,Sebastian H. Scharf,David A. Schubert,Klas Hatje,Nadege Pelletier,Olivia Spleiss,John C. Reed +11 more
TL;DR: A greater understanding of tissue-specific immunoregulation, namely, "tissue- specific immunostats," is called for to make advances in treatments for cancer.
Journal ArticleDOI
Nanocage-Therapeutics Prevailing Phagocytosis and Immunogenic Cell Death Awakens Immunity against Cancer
Eunjung Lee,Eunjung Lee,Gi Hoon Nam,Gi Hoon Nam,Na Kyeong Lee,Na Kyeong Lee,Minwoo Kih,Minwoo Kih,Eunee Koh,Eunee Koh,Yoon Kyoung Kim,Yoon Kyoung Kim,Yeonsun Hong,Yeonsun Hong,Soyoun Kim,Seung Yoon Park,Cherlhyun Jeong,Yoosoo Yang,In San Kim,In San Kim +19 more
TL;DR: A novel tactic is reported for overcoming the activation‐energy threshold of the immunosuppressive tumor microenvironment and mediating the delivery and presentation of tumor neoantigens to the host's immune system.
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.
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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.
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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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