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1 September 2020
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Although PD-1 blockade has become a mainstay treatment for melanoma, it is not always effective. In a patient with metastatic melanoma in which all tumors but one responded to PD-1 blockade, Gstalder and colleagues found that the tumor-suppressor gene FBXW7 had a loss-of-function mutation. In immuno-competent mice, Fbxw7 deficiency in melanomas disrupted double-stranded RNA (dsRNA)–sensing pathways, leading to alterations in the tumor immune microenvironment that included a decrease in the CD8+ T-cell infiltration that PD-1 blockade normally induces. Restoration of dsRNA sensing in these melanomas conferred sensitivity to anti–PD-1. This work suggests that reactivation of dsRNA-sensing pathways in patients with FBXW7-mutant melanoma may be therapeutically relevant. For more information, see the article by Gstalder and colleagues on page 1296.Close Modal - PDF Icon PDF LinkTable of Contents
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ISSN 2159-8274
EISSN 2159-8290
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Research Brief
Changes in Aged Fibroblast Lipid Metabolism Induce Age-Dependent Melanoma Cell Resistance to Targeted Therapy via the Fatty Acid Transporter FATP2
Gretchen M. Alicea; Vito W. Rebecca; Aaron R. Goldman; Mitchell E. Fane; Stephen M. Douglass; Reeti Behera; Marie R. Webster; Curtis H. Kugel, III; Brett L. Ecker; M. Cecilia Caino; Andrew V. Kossenkov; Hsin-Yao Tang; Dennie T. Frederick; Keith T. Flaherty; Xiaowei Xu; Qin Liu; Dmitry I. Gabrilovich; Meenhard Herlyn; Ian A. Blair; Zachary T. Schug; David W. Speicher; Ashani T. Weeraratna
Research Articles
Inactivation of Fbxw7 Impairs dsRNA Sensing and Confers Resistance to PD-1 Blockade
Cécile Gstalder; David Liu; Diana Miao; Bart Lutterbach; Alexander L. DeVine; Chenyu Lin; Megha Shettigar; Priya Pancholi; Elizabeth I. Buchbinder; Scott L. Carter; Michael P. Manos; Vanesa Rojas-Rudilla; Ryan Brennick; Evisa Gjini; Pei-Hsuan Chen; Ana Lako; Scott Rodig; Charles H. Yoon; Gordon J. Freeman; David A. Barbie; F. Stephen Hodi; Wayne Miles; Eliezer M. Van Allen; Rizwan Haq
Epigenetic Switch–Induced Viral Mimicry Evasion in Chemotherapy-Resistant Breast Cancer
Geneviève Deblois; Seyed Ali Madani Tonekaboni; Giacomo Grillo; Constanza Martinez; Yunchi Ingrid Kao; Felicia Tai; Ilias Ettayebi; Anne-Marie Fortier; Paul Savage; Alexandra N. Fedor; Xiaojing Liu; Paul Guilhamon; Evelyne Lima-Fernandes; Alex Murison; Hellen Kuasne; Wail Ba-alawi; David W. Cescon; Cheryl H. Arrowsmith; Daniel D. De Carvalho; Benjamin Haibe-Kains; Jason W. Locasale; Morag Park; Mathieu Lupien
Author Choice
Single-Cell Analysis Reveals Fibroblast Clusters Linked to Immunotherapy Resistance in Cancer
Yann Kieffer; Hocine R. Hocine; Géraldine Gentric; Floriane Pelon; Charles Bernard; Brigitte Bourachot; Sonia Lameiras; Luca Albergante; Claire Bonneau; Alice Guyard; Karin Tarte; Andrei Zinovyev; Sylvain Baulande; Gerard Zalcman; Anne Vincent-Salomon; Fatima Mechta-Grigoriou
Limited Environmental Serine and Glycine Confer Brain Metastasis Sensitivity to PHGDH Inhibition
Bryan Ngo; Eugenie Kim; Victoria Osorio-Vasquez; Sophia Doll; Sophia Bustraan; Roger J. Liang; Alba Luengo; Shawn M. Davidson; Ahmed Ali; Gino B. Ferraro; Grant M. Fischer; Roozbeh Eskandari; Diane S. Kang; Jing Ni; Ariana Plasger; Vinagolu K. Rajasekhar; Edward R. Kastenhuber; Sarah Bacha; Roshan K. Sriram; Benjamin D. Stein; Samuel F. Bakhoum; Matija Snuderl; Paolo Cotzia; John H. Healey; Nello Mainolfi; Vipin Suri; Adam Friedman; Mark Manfredi; David M. Sabatini; Drew R. Jones; Min Yu; Jean J. Zhao; Rakesh K. Jain; Kayvan R. Keshari; Michael A. Davies; Matthew G. Vander Heiden; Eva Hernando; Matthias Mann; Lewis C. Cantley; Michael E. Pacold
Chromatin Regulator CHD1 Remodels the Immunosuppressive Tumor Microenvironment in PTEN-Deficient Prostate Cancer
Di Zhao; Li Cai; Xin Lu; Xin Liang; Jiexi Li; Peiwen Chen; Michael Ittmann; Xiaoying Shang; Shan Jiang; Haoyan Li; Chenling Meng; Ivonne Flores; Jian H. Song; James W. Horner; Zhengdao Lan; Chang-Jiun Wu; Jun Li; Qing Chang; Ko-Chien Chen; Guocan Wang; Pingna Deng; Denise J. Spring; Y. Alan Wang; Ronald A. DePinho
Posttranslational Regulation of the Exon Skipping Machinery Controls Aberrant Splicing in Leukemia
Yalu Zhou; Cuijuan Han; Eric Wang; Adam H. Lorch; Valentina Serafin; Byoung-Kyu Cho; Blanca T. Gutierrez Diaz; Julien Calvo; Celestia Fang; Alireza Khodadadi-Jamayran; Tommaso Tabaglio; Christian Marier; Anna Kuchmiy; Limin Sun; George Yacu; Szymon K. Filip; Qi Jin; Yoh-Hei Takahashi; David R. Amici; Emily J. Rendleman; Radhika Rawat; Silvia Bresolin; Maddalena Paganin; Cheng Zhang; Hu Li; Irawati Kandela; Yuliya Politanska; Hiam Abdala-Valencia; Marc L. Mendillo; Ping Zhu; Bruno Palhais; Pieter Van Vlierberghe; Tom Taghon; Iannis Aifantis; Young Ah Goo; Ernesto Guccione; Adriana Heguy; Aristotelis Tsirigos; Keng Boon Wee; Rama K. Mishra; Francoise Pflumio; Benedetta Accordi; Giuseppe Basso; Panagiotis Ntziachristos
RBMS1 Suppresses Colon Cancer Metastasis through Targeted Stabilization of Its mRNA Regulon
Johnny Yu; Albertas Navickas; Hosseinali Asgharian; Bruce Culbertson; Lisa Fish; Kristle Garcia; John Paolo Olegario; Maria Dermit; Martin Dodel; Benjamin Hänisch; Yikai Luo; Ethan M. Weinberg; Rodrigo Dienstmann; Robert S. Warren; Faraz K. Mardakheh; Hani Goodarzi
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