Inhibiting DNA Methylation Causes an Interferon Response in Cancer via dsRNA Including Endogenous Retroviruses
Katherine B. Chiappinelli,Pamela L. Strissel,Alexis Desrichard,Huili Li,Christine Henke,Benjamin Akman,Alexander Hein,Neal S. Rote,Leslie Cope,Alexandra Snyder,Vladimir Makarov,Sadna Budhu,Dennis J. Slamon,Jedd D. Wolchok,Drew M. Pardoll,Matthias W. Beckmann,Cynthia A. Zahnow,Taha Merghoub,Timothy A. Chan,Stephen B. Baylin,Reiner Strick +20 more
TL;DR: In melanoma patients treated with an immune checkpoint therapy, high viral defense signature expression in tumors significantly associates with durable clinical response and DNMTi treatment sensitizes to anti-CTLA4 therapy in a pre-clinical melanoma model.
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About: This article is published in Cell. The article was published on 27 Aug 2015. and is currently open access. The article focuses on the topics: Interferon type I & Endogenous retrovirus.
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Citations
Discovery Proteomics Analysis Determines That Driver Oncogenes Suppress Antiviral Defense Pathways Through Reduction in Interferon-β Autocrine Stimulation
Paige Solomon,Lisa L. Kirkemo,Gary M. Wilson,Kevin Leung,Mark H. Almond,Leanne C. Sayles,E. Alejandro Sweet-Cordero,Oren S. Rosenberg,Joshua J. Coon,James A. Wells +9 more
TL;DR: In this paper , the authors explored how cellular proteomes are remodeled in isogenic cell lines engineered with or without these driver oncogenes using a reductionist approach and found that the oncogenees reduced basal expression of and autocrine stimulation by type 1 interferon causing remarkable convergence on common phenotypic and functional profiles.
7
Human LINE-1 retrotransposons: impacts on the genome and regulation by host factors.
TL;DR: In this paper , the authors summarize the known host proteins that regulate L1 activity at different stages of the replication cycle and discuss how these factors modulate disease-associated phenotypes caused by L1.
GAS-STING: a classical DNA recognition pathways to tumor therapy
Xinrui Wang,Meijia Lin,Liping Zhu,Zhoujie Ye +3 more
TL;DR: The role of type I IFNs in the articulation between innate immunity and T-cell antitumour immunity and the mechanism and biological function in traditional tumor therapy and immunotherapy are discussed.
7
Epigenomic reprogramming of repetitive noncoding RNAs and IFN-stimulated genes by mutant KRAS
Roman E. Reggiardo,Maroli Sv,Haley Halasz,Mehmet Ozgun Ozen,Carrillo D,Erin LaMontagne,Lila Whitehead,Eejung Kim,Malik S,Jason D Fernandes,Georgi K. Marinov,Collisson E,Utkan Demirci,Daniel H. Kim +13 more
TL;DR: The results reveal that mutant KRAS remodels the noncoding transcriptome through epigenomic reprogramming, expanding the scope of genomic elements regulated by this fundamental signaling pathway and revealing how mutantKRAS induces an intrinsic IFN-stimulated gene signature often seen in ADAR-dependent cancers.
Targeting protein kinases benefits cancer immunotherapy.
TL;DR: In this paper , the authors comprehensively summarize the role of protein kinases in modulating immune checkpoints both in tumor and immune cells, and reshaping tumor immune microenvironments by evoking innate immune response and neoantigen generation or presentation.
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PD-1 Blockade in Tumors with Mismatch-Repair Deficiency
Dung T. Le,Jennifer N. Uram,Hao Wang,Bjarne Bartlett,Holly Kemberling,Aleksandra Eyring,Andrew D. Skora,Brandon Luber,Nilofer S. Azad,Daniel A. Laheru,Barbara A. Biedrzycki,Ross C. Donehower,Atif Zaheer,George A. Fisher,Todd S. Crocenzi,James J. Lee,Steven M. Duffy,Richard M. Goldberg,Richard M. Goldberg,Albert de la Chapelle,Albert de la Chapelle,Minori Koshiji,Feriyl Bhaijee,Thomas Huebner,Ralph H. Hruban,Laura D. Wood,Nathan Cuka,Drew M. Pardoll,Nickolas Papadopoulos,Kenneth W. Kinzler,Shibin Zhou,Toby C. Cornish,Janis M. Taube,Robert A. Anders,James R. Eshleman,Bert Vogelstein,Luis A. Diaz +36 more
TL;DR: This study showed that mismatch-repair status predicted clinical benefit of immune checkpoint blockade with pembrolizumab, and high somatic mutation loads were associated with prolonged progression-free survival.
Safety and Activity of Anti–PD-L1 Antibody in Patients with Advanced Cancer
Julie R. Brahmer,Scott S. Tykodi,Scott S. Tykodi,Laura Q.M. Chow,Wen-Jen Hwu,Suzanne L. Topalian,Patrick Hwu,Charles G. Drake,Luis H. Camacho,John S. Kauh,Kunle Odunsi,Henry C. Pitot,Omid Hamid,Shailender Bhatia,Renato G. Martins,Keith D. Eaton,Shuming Chen,Theresa M. Salay,Suresh Alaparthy,Joseph F. Grosso,Alan J. Korman,Susan M. Parker,Shruti Agrawal,Stacie M. Goldberg,Drew M. Pardoll,Ashok Kumar Gupta,Jon M. Wigginton +26 more
TL;DR: Antibody-mediated blockade of PD-L1 induced durable tumor regression and prolonged stabilization of disease in patients with advanced cancers, including non-small-cell lung cancer, melanoma, and renal-cell cancer.
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