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1 June 2021
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Cover Image
To escape immune checkpoint blockade's antitumor effects, some cancers downregulate MHC-I, reducing antigen presentation. Gu, Zhang, Wang, Jiang, and colleagues found that TRAF3, a cytoplasmic signal-transduction protein and NFκB pathway inhibitor, was a negative regulator of MHC-I expression. Traf3-knockout mice exhibited enhanced T cell–mediated cytotoxicity toward tumor cells, and immune checkpoint blockade efficacy was enhanced in these mice. Traf3 knockout also resulted in a distinctive transcriptional profile that correlated with the transcriptional profiles of human melanomas that had greater MHC-I expression; patients with these profiles had better median survival. Finally, a drug screen identified birinapant as being capable of mimicking the effects of Traf3 knockout in mice. For more information, see the article by Gu, Zhang, Wang, Jiang, and colleagues on page 1524. - PDF Icon PDF LinkTable of Contents
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ISSN 2159-8274
EISSN 2159-8290
In This Issue
News in Brief
News in Depth
Research Watch
Metastasis
Epigenetics
Metabolism
Structural Biology
Leukemia
Clinical Trials
Microbiome
Lymphoma
Immunotherapy
Letter to the Editor
In the Spotlight
Perspective
Reviews
Research Briefs
LKB1/STK11 Is a Tumor Suppressor in the Progression of Myeloproliferative Neoplasms
Christian Marinaccio; Praveen Suraneni; Hamza Celik; Andrew Volk; Qiang Jeremy Wen; Te Ling; Marinka Bulic; Terra Lasho; Richard P. Koche; Christopher A. Famulare; Noushin Farnoud; Brady Stein; Michael Schieber; Sandeep Gurbuxani; David E. Root; Scott T. Younger; Ronald Hoffman; Naseema Gangat; Panagiotis Ntziachristos; Navdeep S. Chandel; Ross L. Levine; Raajit K. Rampal; Grant A. Challen; Ayalew Tefferi; John D. Crispino
Loss of LKB1 (also known as STK11) was associated with progression of myeloproliferative neoplasms (MPN) to blast-phase MPN, a serious manifestation of acute myeloid leukemia in mouse models and in patients.
Author Choice
TNIK Is a Therapeutic Target in Lung Squamous Cell Carcinoma and Regulates FAK Activation through Merlin
Pedro Torres-Ayuso; Elvira An; Katherine M. Nyswaner; Ryan C. Bensen; Daniel A. Ritt; Suzanne I. Specht; Sudipto Das; Thorkell Andresson; Raul E. Cachau; Roger J. Liang; Amy L. Ries; Christina M. Robinson; Simone Difilippantonio; Brad Gouker; Laura Bassel; Baktiar O. Karim; Chad J. Miller; Benjamin E. Turk; Deborah K. Morrison; John Brognard
Research Articles
Matched Targeted Therapy for Pediatric Patients with Relapsed, Refractory, or High-Risk Leukemias: A Report from the LEAP Consortium
Yana Pikman; Sarah K. Tasian; Maria Luisa Sulis; Kristen Stevenson; Traci M. Blonquist; Beth Apsel Winger; Todd M. Cooper; Melinda Pauly; Kelly W. Maloney; Michael J. Burke; Patrick A. Brown; Nathan Gossai; Jennifer L. McNeer; Neerav N. Shukla; Peter D. Cole; Justine M. Kahn; Jing Chen; Matthew J. Barth; Jeffrey A. Magee; Lisa Gennarini; Asmani A. Adhav; Catherine M. Clinton; Nicole Ocasio-Martinez; Giacomo Gotti; Yuting Li; Shan Lin; Alma Imamovic; Cristina E. Tognon; Tasleema Patel; Haley L. Faust; Cristina F. Contreras; Anjali Cremer; Wilian A. Cortopassi; Diego Garrido Ruiz; Matthew P. Jacobson; Neekesh V. Dharia; Angela Su; Amanda L. Robichaud; Amy Saur Conway; Katherine Tarlock; Elliot Stieglitz; Andrew E. Place; Alexandre Puissant; Stephen P. Hunger; Annette S. Kim; Neal I. Lindeman; Lia Gore; Katherine A. Janeway; Lewis B. Silverman; Jeffrey W. Tyner; Marian H. Harris; Mignon L. Loh; Kimberly Stegmaier
Author Choice
Venetoclax and Navitoclax in Combination with Chemotherapy in Patients with Relapsed or Refractory Acute Lymphoblastic Leukemia and Lymphoblastic Lymphoma
Vinod A. Pullarkat; Norman J. Lacayo; Elias Jabbour; Jeffrey E. Rubnitz; Ashish Bajel; Theodore W. Laetsch; Jessica Leonard; Susan I. Colace; Seong Lin Khaw; Shaun A. Fleming; Ryan J. Mattison; Robin Norris; Joseph T. Opferman; Kathryn G. Roberts; Yaqi Zhao; Chunxu Qu; Mohamed Badawi; Michelle Schmidt; Bo Tong; John C. Pesko; Yan Sun; Jeremy A. Ross; Deeksha Vishwamitra; Lindsey Rosenwinkel; Su Young Kim; Amanda Jacobson; Charles G. Mullighan; Thomas B. Alexander; Wendy Stock
Mutations in the RAS/MAPK Pathway Drive Replication Repair–Deficient Hypermutated Tumors and Confer Sensitivity to MEK Inhibition
Brittany B. Campbell; Melissa A. Galati; Simone C. Stone; Alexandra N. Riemenschneider; Melissa Edwards; Sumedha Sudhaman; Robert Siddaway; Martin Komosa; Nuno M. Nunes; Liana Nobre; A. Sorana Morrissy; Matthew Zatzman; Michal Zapotocky; Lazar Joksimovic; Sangeetha N. Kalimuthu; David Samuel; Gary Mason; Eric Bouffet; Daniel A. Morgenstern; Melyssa Aronson; Carol Durno; David Malkin; John M. Maris; Michael D. Taylor; Adam Shlien; Trevor J. Pugh; Pamela S. Ohashi; Cynthia E. Hawkins; Uri Tabori
Author Choice
Clinical and Biological Subtypes of B-cell Lymphoma Revealed by Microenvironmental Signatures
Nikita Kotlov; Alexander Bagaev; Maria V. Revuelta; Jude M. Phillip; Maria Teresa Cacciapuoti; Zoya Antysheva; Viktor Svekolkin; Ekaterina Tikhonova; Natalia Miheecheva; Natalia Kuzkina; Grigorii Nos; Fabrizio Tabbo; Felix Frenkel; Paola Ghione; Maria Tsiper; Nava Almog; Nathan Fowler; Ari M. Melnick; John P. Leonard; Giorgio Inghirami; Leandro Cerchietti
Author Choice
Nongenetic Evolution Drives Lung Adenocarcinoma Spatial Heterogeneity and Progression
Daniele Tavernari; Elena Battistello; Elie Dheilly; Aaron S. Petruzzella; Marco Mina; Jessica Sordet-Dessimoz; Solange Peters; Thorsten Krueger; David Gfeller; Nicolo Riggi; Elisa Oricchio; Igor Letovanec; Giovanni Ciriello
Identification and Therapeutic Targeting of GPR20, Selectively Expressed in Gastrointestinal Stromal Tumors, with DS-6157a, a First-in-Class Antibody–Drug Conjugate
Kenji Iida; Amr H. Abdelhamid Ahmed; Akiko Kawano Nagatsuma; Tomoko Shibutani; Satoru Yasuda; Michiko Kitamura; Chiharu Hattori; Manabu Abe; Jun Hasegawa; Takuma Iguchi; Tsuyoshi Karibe; Takashi Nakada; Koichiro Inaki; Reiko Kamei; Yuki Abe; Taisei Nomura; Jessica L. Andersen; Sandro Santagata; Matthew L. Hemming; Suzanne George; Toshihiko Doi; Atsushi Ochiai; George D. Demetri; Toshinori Agatsuma
Therapeutically Increasing MHC-I Expression Potentiates Immune Checkpoint Blockade
Shengqing Stan Gu; Wubing Zhang; Xiaoqing Wang; Peng Jiang; Nicole Traugh; Ziyi Li; Clifford Meyer; Blair Stewig; Yingtian Xie; Xia Bu; Michael P. Manos; Alba Font-Tello; Evisa Gjini; Ana Lako; Klothilda Lim; Jake Conway; Alok K. Tewari; Zexian Zeng; Avinash Das Sahu; Collin Tokheim; Jason L. Weirather; Jingxin Fu; Yi Zhang; Benjamin Kroger; Jin Hua Liang; Paloma Cejas; Gordon J. Freeman; Scott Rodig; Henry W. Long; Benjamin E. Gewurz; F. Stephen Hodi; Myles Brown; X. Shirley Liu
Author Choice
Chemotherapy Induces Senescence-Like Resilient Cells Capable of Initiating AML Recurrence
Cihangir Duy; Meng Li; Matt Teater; Cem Meydan; Francine E. Garrett-Bakelman; Tak C. Lee; Christopher R. Chin; Ceyda Durmaz; Kimihito C. Kawabata; Eugen Dhimolea; Constantine S. Mitsiades; Hartmut Doehner; Richard J. D'Andrea; Michael W. Becker; Elisabeth M. Paietta; Christopher E. Mason; Martin Carroll; Ari M. Melnick
Author Choice
A CRISPR/Cas9-Engineered ARID1A-Deficient Human Gastric Cancer Organoid Model Reveals Essential and Nonessential Modes of Oncogenic Transformation
Yuan-Hung Lo; Kevin S. Kolahi; Yuhong Du; Chiung-Ying Chang; Andrey Krokhotin; Ajay Nair; Walter D. Sobba; Kasper Karlsson; Sunny J. Jones; Teri A. Longacre; Amanda T. Mah; Bahar Tercan; Alexandra Sockell; Hang Xu; Jose A. Seoane; Jin Chen; Ilya Shmulevich; Jonathan S. Weissman; Christina Curtis; Andrea Califano; Haian Fu; Gerald R. Crabtree; Calvin J. Kuo
Serine Biosynthesis Is a Metabolic Vulnerability in FLT3-ITD–Driven Acute Myeloid Leukemia
Stefan Bjelosevic; Emily Gruber; Andrea Newbold; Carolyn Shembrey; Jennifer R. Devlin; Simon J. Hogg; Lev Kats; Izabela Todorovski; Zheng Fan; Thomas C. Abrehart; Giovanna Pomilio; Andrew Wei; Gareth P. Gregory; Stephin J. Vervoort; Kristin K. Brown; Ricky W. Johnstone
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