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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Blockage of immune checkpoint molecules increases T-cell priming potential of dendritic cell vaccine.
Hadi Hassannia,Hadi Hassannia,Mitra Ghasemi Chaleshtari,Fatemeh Atyabi,Mahshid Nosouhian,Ali Masjedi,Mohammad Hojjat-Farsangi,Mohammad Hojjat-Farsangi,Afshin Namdar,Gholamreza Azizi,Hamed Mohammadi,Ghasem Ghalamfarsa,Gholamabas Sabz,Sajad Hasanzadeh,Mehdi Yousefi,Farhad Jadidi-Niaragh +15 more
TL;DR: The findings imply that PD‐L1‐silenced DCs can be considered as a potent immunotherapeutic approach in combination with PD‐1‐siRNA loaded NPs, however; further in vivo investigation is required in animal models.
Journal ArticleDOI
Expression patterns of programmed death ligand 1 correlate with different microenvironments and patient prognosis in hepatocellular carcinoma.
Chao-Qun Liu,Jing Xu,Zhong-Guo Zhou,Li-Lian Jin,Xing-Juan Yu,Gang Xiao,Jie Lin,Shi-Mei Zhuang,Yaojun Zhang,Limin Zheng +9 more
TL;DR: This study provided a novel methodology to evaluate PD-L 1 expression in the tumour microenvironment, which might help to select patients who would benefit from anti-PD-1/PD-L1 immunotherapies.
Journal ArticleDOI
Oncolytic Adenovirus: Strategies and Insights for Vector Design and Immuno-Oncolytic Applications
TL;DR: Significant off-target interactions between the viral vector and cellular and proteinaceous components of the bloodstream have been documented that promote uptake into non-target cells and determine dose-limiting toxicities.
Journal ArticleDOI
Invasive lobular and ductal breast carcinoma differ in immune response, protein translation efficiency and metabolism.
Tian Du,Tian Du,Li Zhu,Kevin M. Levine,Nilgun Tasdemir,Adrian V. Lee,Dario A. A. Vignali,Bennett Van Houten,George C. Tseng,Steffi Oesterreich +9 more
TL;DR: The higher immune activity uncovered in ILC highlights the currently unexplored potential of a response to immunotherapy in a subset of patients with ILC, and the lower rates of protein translation and metabolism - known features of tumor dormancy - may play a role in the late recurrences of ILC and lower detection rate in mammography and PET scanning.
Journal ArticleDOI
The role of microbiota in cancer therapy.
TL;DR: This work has shown that the gut microbiota modulates the response by priming for the release of pro-inflammatory factors and reactive oxygen species in cancer therapy and its toxic side effects by targeting the microbiota.
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
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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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