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1 April 2019
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Using a multiomics approach to analyze 347 cases of diffuse large B-cell lymphoma (DLBCL), Ennishi, Takata, and colleagues observed that loss of MHC expression defines a molecular subgroup of germinal center B cell-like DLBCL with reduced T-cell infiltration, an immune-suppressed microenvironment, and poor survival. EZH2 was the most frequently mutated gene in MHC-deficient DLBCL, and Ezh2 mutation in mouse models reduced MHC levels and amounts of T-cell infiltrates and resulted in shorter survival. EZH2 inhibition restored MHC expression in DLBCL cells by reducing repressive histone methylation at the promoters of MHC transactivator genes. These findings identify an EZH2-mediated epigenetic mechanism of immune escape in DLBCL and suggest that EZH2 inhibition could be used to improve responses to immunotherapy. For details, please see the article by Ennishi, Takata, and colleagues on page 546. - PDF Icon PDF LinkTable of Contents
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ISSN 2159-8274
EISSN 2159-8290
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Detection and Surveillance of Bladder Cancer Using Urine Tumor DNA
Jonathan C. Dudley; Joseph Schroers-Martin; Daniel V. Lazzareschi; William Y. Shi; Simon B. Chen; Mohammad S. Esfahani; Dharati Trivedi; Jacob J. Chabon; Aadel A. Chaudhuri; Henning Stehr; Chih Long Liu; Harumi Lim; Helio A. Costa; Barzin Y. Nabet; Mandy L.Y. Sin; Joseph C. Liao; Ash A. Alizadeh; Maximilian Diehn
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Transcriptomic Profiling of the Tumor Microenvironment Reveals Distinct Subgroups of Clear Cell Renal Cell Cancer: Data from a Randomized Phase III Trial
A. Ari Hakimi; Martin H. Voss; Fengshen Kuo; Alejandro Sanchez; Ming Liu; Briana G. Nixon; Lynda Vuong; Irina Ostrovnaya; Ying-Bei Chen; Victor Reuter; Nadeem Riaz; Yuan Cheng; Parul Patel; Mahtab Marker; Albert Reising; Ming O. Li; Timothy A. Chan; Robert J. Motzer
MAPK Pathway Suppression Unmasks Latent DNA Repair Defects and Confers a Chemical Synthetic Vulnerability in BRAF-, NRAS-, and NF1-Mutant Melanomas
Ophélia Maertens; Ryan Kuzmickas; Haley E. Manchester; Chloe E. Emerson; Alessandra G. Gavin; Caroline J. Guild; Terence C. Wong; Thomas De Raedt; Christian Bowman-Colin; Elodie Hatchi; Levi A. Garraway; Keith T. Flaherty; Shailja Pathania; Stephen J. Elledge; Karen Cichowski
Molecular and Genetic Characterization of MHC Deficiency Identifies EZH2 as Therapeutic Target for Enhancing Immune Recognition
Daisuke Ennishi; Katsuyoshi Takata; Wendy Béguelin; Gerben Duns; Anja Mottok; Pedro Farinha; Ali Bashashati; Saeed Saberi; Merrill Boyle; Barbara Meissner; Susana Ben-Neriah; Bruce W. Woolcock; Adèle Telenius; Daniel Lai; Matt Teater; Robert Kridel; Kerry J. Savage; Laurie H. Sehn; Ryan D. Morin; Marco A. Marra; Sohrab P. Shah; Joseph M. Connors; Randy D. Gascoyne; David W. Scott; Ari M. Melnick; Christian Steidl
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