Browse Articles

  • Letter |

    Myeloid-derived suppressor cells are induced in newborn mice by breast-milk-derived lactoferrin and confer protection in a model of necrotizing enterocolitis. Their frequency and suppressive activity is decreased in very low-weight infants.

    • Yu-Mei He
    • , Xing Li
    • , Michela Perego
    • , Yulia Nefedova
    • , Andrew V Kossenkov
    • , Erik A Jensen
    • , Valerian Kagan
    • , Yu-Feng Liu
    • , Shu-Yu Fu
    • , Qing-Jian Ye
    • , Yan-Hong Zhou
    • , Lai Wei
    • , Dmitry I Gabrilovich
    •  & Jie Zhou
  • Article |

    Complete vaccine-mediated immune control of highly pathogenic Mycobacterium tuberculosis is possible if immune effector responses can intercept the infection at its earliest stages.

    • Scott G Hansen
    • , Daniel E Zak
    • , Guangwu Xu
    • , Julia C Ford
    • , Emily E Marshall
    • , Daniel Malouli
    • , Roxanne M Gilbride
    • , Colette M Hughes
    • , Abigail B Ventura
    • , Emily Ainslie
    • , Kurt T Randall
    • , Andrea N Selseth
    • , Parker Rundstrom
    • , Lauren Herlache
    • , Matthew S Lewis
    • , Haesun Park
    • , Shannon L Planer
    • , John M Turner
    • , Miranda Fischer
    • , Christina Armstrong
    • , Robert C Zweig
    • , Joseph Valvo
    • , Jackie M Braun
    • , Smitha Shankar
    • , Lenette Lu
    • , Andrew W Sylwester
    • , Alfred W Legasse
    • , Martin Messerle
    • , Michael A Jarvis
    • , Lynn M Amon
    • , Alan Aderem
    • , Galit Alter
    • , Dominick J Laddy
    • , Michele Stone
    • , Aurelio Bonavia
    • , Thomas G Evans
    • , Michael K Axthelm
    • , Klaus Früh
    • , Paul T Edlefsen
    •  & Louis J Picker
  • Article |

    Peter Scacheri and colleagues report that the activity of enhancer elements in metastatic osteosarcoma is distinct from that in primary tumors and plays a functional role in metastatic progression of osteosarcoma.

    • James J Morrow
    • , Ian Bayles
    • , Alister P W Funnell
    • , Tyler E Miller
    • , Alina Saiakhova
    • , Michael M Lizardo
    • , Cynthia F Bartels
    • , Maaike Y Kapteijn
    • , Stevephen Hung
    • , Arnulfo Mendoza
    • , Gursimran Dhillon
    • , Daniel R Chee
    • , Jay T Myers
    • , Frederick Allen
    • , Marco Gambarotti
    • , Alberto Righi
    • , Analisa DiFeo
    • , Brian P Rubin
    • , Alex Y Huang
    • , Paul S Meltzer
    • , Lee J Helman
    • , Piero Picci
    • , Henri Versteeg
    • , John Stamatoyannopolus
    • , Chand Khanna
    •  & Peter C Scacheri
  • Article |

    A small molecule selectively targeting the cell-surface glutamine transporter ASCT2 disrupts glutamine signaling and metabolism. This compound displays low toxicity and strong antitumor activity in preclinical in vitro and in vivo models, thus holding promise as a treatment for glutamine-dependent tumors in a clinical setting.

    • Michael L Schulte
    • , Allie Fu
    • , Ping Zhao
    • , Jun Li
    • , Ling Geng
    • , Shannon T Smith
    • , Jumpei Kondo
    • , Robert J Coffey
    • , Marc O Johnson
    • , Jeffrey C Rathmell
    • , Joe T Sharick
    • , Melissa C Skala
    • , Jarrod A Smith
    • , Jordan Berlin
    • , M Kay Washington
    • , Michael L Nickels
    •  & H Charles Manning
  • Article |

    Expression of AXL earmarks melanoma cells resistant to BRAF and MEK inhibitors that either pre-exist in treatment-naive tumors or emerge in response to therapy. The combination of an AXL-MMAE antibody-drug conjugate with BRAF and MEK inhibitors eliminates heterogeneous melanoma cell populations and prolongs survival in experimental in vivo models at tolerable toxicity. This approach is currently being tested in clinical trials and provides insights into the therapeutic targeting of intra-tumor heterogeneity.

    • Julia Boshuizen
    • , Louise A Koopman
    • , Oscar Krijgsman
    • , Aida Shahrabi
    • , Elke Gresnigt– van den Heuvel
    • , Maarten A Ligtenberg
    • , David W Vredevoogd
    • , Kristel Kemper
    • , Thomas Kuilman
    • , Ji-Ying Song
    • , Nora Pencheva
    • , Jens Thing Mortensen
    • , Marnix Geukes Foppen
    • , Elisa A Rozeman
    • , Christian U Blank
    • , Maarten L Janmaat
    • , David Satijn
    • , Esther C W Breij
    • , Daniel S Peeper
    •  & Paul W H I Parren
  • Article |

    Hyer et al. generate a potent and specific small-molecule inhibitor of the E1 ubiquitin-activating enzyme UBE1 that has antitumor activity in mice against a wide variety of tumor types.

    • Marc L Hyer
    • , Michael A Milhollen
    • , Jeff Ciavarri
    • , Paul Fleming
    • , Tary Traore
    • , Darshan Sappal
    • , Jessica Huck
    • , Judy Shi
    • , James Gavin
    • , Jim Brownell
    • , Yu Yang
    • , Bradley Stringer
    • , Robert Griffin
    • , Frank Bruzzese
    • , Teresa Soucy
    • , Jennifer Duffy
    • , Claudia Rabino
    • , Jessica Riceberg
    • , Kara Hoar
    • , Anya Lublinsky
    • , Saurabh Menon
    • , Michael Sintchak
    • , Nancy Bump
    • , Sai M Pulukuri
    • , Steve Langston
    • , Stephen Tirrell
    • , Mike Kuranda
    • , Petter Veiby
    • , John Newcomb
    • , Ping Li
    • , Jing Tao Wu
    • , Josh Powe
    • , Lawrence R Dick
    • , Paul Greenspan
    • , Katherine Galvin
    • , Mark Manfredi
    • , Chris Claiborne
    • , Benjamin S Amidon
    •  & Neil F Bence
  • News & Views |

    A Children's Oncology Group study of nearly 1,000 pediatric acute myeloid leukemia (AML) cases reveals marked differences between the genomic landscapes of pediatric and adult AML and offers directions for future work.

    • Andrew M Brunner
    •  & Timothy A Graubert
  • News & Views |

    In a recent study of hepatic ischemia–reperfusion injury (IRI), Zhang et al. use tandem 'omics' approaches in mice, pigs, and nonhuman primates to identify lipid metabolic reprogramming as a key determinant of IRI, thus providing novel mechanistic and therapeutic insights.

    • Satdarshan P Monga
  • Editorial |

    Mental illnesses impose a grave disease burden worldwide, yet progress in managing and treating them has largely stalled. Harnessing the power of big data may break the current impasse and open new avenues for better diagnosis, treatment and prevention of these devastating illnesses.

  • Article |

    Pier Paolo Pandolfi and colleagues report that the genetic background of tumors in mice recruits specific immune-cell subsets, suggesting that precision medicine should account for both the tumor drivers and the distinct immune-cell microenvironments that they elicit.

    • Marco Bezzi
    • , Nina Seitzer
    • , Tomoki Ishikawa
    • , Markus Reschke
    • , Ming Chen
    • , Guocan Wang
    • , Caitlin Mitchell
    • , Christopher Ng
    • , Jesse Katon
    • , Andrea Lunardi
    • , Sabina Signoretti
    • , John G Clohessy
    • , Jiangwen Zhang
    •  & Pier Paolo Pandolfi
  • Letter |

    Platelet activation after muscle trauma promotes extracellular trap release by macrophages and acute kidney injury.

    • Koshu Okubo
    • , Miho Kurosawa
    • , Mako Kamiya
    • , Yasuteru Urano
    • , Akari Suzuki
    • , Kazuhiko Yamamoto
    • , Koji Hase
    • , Koichiro Homma
    • , Junichi Sasaki
    • , Hiroaki Miyauchi
    • , Tatsuo Hoshino
    • , Matsuhiko Hayashi
    • , Tanya N Mayadas
    •  & Junichi Hirahashi
  • Article |

    Among many populations of blood cells, high dimensional analysis using mass cytometry reveals classical monocyte frequency as strong predictors of response to PD-1 blockade therapy of melanoma.

    • Carsten Krieg
    • , Malgorzata Nowicka
    • , Silvia Guglietta
    • , Sabrina Schindler
    • , Felix J Hartmann
    • , Lukas M Weber
    • , Reinhard Dummer
    • , Mark D Robinson
    • , Mitchell P Levesque
    •  & Burkhard Becher
  • Letter |

    A luteinizing hormone–releasing hormone antagonist, used clinically for sex-steroid inhibition, promotes quiescence of hematopoietic stem cells and thereby promotes hematopoietic recovery and survival of lethally irradiated mice.

    • Enrico Velardi
    • , Jennifer J Tsai
    • , Stefan Radtke
    • , Kirsten Cooper
    • , Kimon V Argyropoulos
    • , Shieh Jae-Hung
    • , Lauren F Young
    • , Amina Lazrak
    • , Odette M Smith
    • , Sophie Lieberman
    • , Fabiana Kreines
    • , Yusuke Shono
    • , Tobias Wertheimer
    • , Robert R Jenq
    • , Alan M Hanash
    • , Prema Narayan
    • , Zhenmin Lei
    • , Malcolm A Moore
    • , Hans-Peter Kiem
    • , Marcel R M van den Brink
    •  & Jarrod A Dudakov
  • Article |

    The deubiquitinase CYLD regulates a TAK1–JNK pathway and can be targeted to ameliorate nonalcoholic steatohepatitis.

    • Yan-Xiao Ji
    • , Zan Huang
    • , Xia Yang
    • , Xiaozhan Wang
    • , Ling-Ping Zhao
    • , Pi-Xiao Wang
    • , Xiao-Jing Zhang
    • , Michele Alves-Bezerra
    • , Lin Cai
    • , Peng Zhang
    • , Yue-Xin Lu
    • , Lan Bai
    • , Mao-Mao Gao
    • , Huan Zhao
    • , Song Tian
    • , Yong Wang
    • , Zhi-Xiang Huang
    • , Xue-Yong Zhu
    • , Yan Zhang
    • , Jun Gong
    • , Zhi-Gang She
    • , Feng Li
    • , David E Cohen
    •  & Hongliang Li
  • Article |

    A recurrent ECSIT mutation in individuals with extranodal natural killer/T cell lymphoma induces NFκB in cancer cells, leading to macrophage activation, and associates with progression to fatal hemophagocytic syndrome. NFκB-targeting therapy produced stable remission in two patients.

    • Haijun Wen
    • , Huajuan Ma
    • , Qichun Cai
    • , Suxia Lin
    • , Xinxing Lei
    • , Bin He
    • , Sijin Wu
    • , Zifeng Wang
    • , Yan Gao
    • , Wensheng Liu
    • , Weiping Liu
    • , Qian Tao
    • , Zijie Long
    • , Min Yan
    • , Dali Li
    • , Keith W. Kelley
    • , Yongliang Yang
    • , Huiqiang Huang
    •  & Quentin Liu
  • Article |

    A proteolytically derived fragment of the epigenetic regulator HDAC4 protects the heart through transcriptional repression of the hexosamine biosynthetic pathway, thereby inhibiting protein O-GlcNAcylation and maintaining normal calcium handling and contractility of cardiomyocytes.

    • Lorenz H Lehmann
    • , Zegeye H Jebessa
    • , Michael M Kreusser
    • , Axel Horsch
    • , Tao He
    • , Mariya Kronlage
    • , Matthias Dewenter
    • , Viviana Sramek
    • , Ulrike Oehl
    • , Jutta Krebs-Haupenthal
    • , Albert H von der Lieth
    • , Andrea Schmidt
    • , Qiang Sun
    • , Julia Ritterhoff
    • , Daniel Finke
    • , Mirko Völkers
    • , Andreas Jungmann
    • , Sven W Sauer
    • , Christian Thiel
    • , Alexander Nickel
    • , Michael Kohlhaas
    • , Michaela Schäfer
    • , Carsten Sticht
    • , Christoph Maack
    • , Norbert Gretz
    • , Michael Wagner
    • , Ali El-Armouche
    • , Lars S Maier
    • , Juan E Camacho Londoño
    • , Benjamin Meder
    • , Marc Freichel
    • , Hermann-Josef Gröne
    • , Patrick Most
    • , Oliver J Müller
    • , Stephan Herzig
    • , Eileen E M Furlong
    • , Hugo A Katus
    •  & Johannes Backs
  • Resource |

    A comprehensive molecular analysis of almost 1,000 pediatric subjects with acute myeloid leukemia (AML) uncovers widespread differences in pediatric AML as compared to adult AML, including a higher frequency of structural variants and different mutational patterns and epigenetic signatures. Future studies are needed to characterize the functional relevance of these alterations and to explore age-tailored therapies to improve disease control in younger patients.

    • Hamid Bolouri
    • , Jason E Farrar
    • , Timothy Triche Jr
    • , Rhonda E Ries
    • , Emilia L Lim
    • , Todd A Alonzo
    • , Yussanne Ma
    • , Richard Moore
    • , Andrew J Mungall
    • , Marco A Marra
    • , Jinghui Zhang
    • , Xiaotu Ma
    • , Yu Liu
    • , Yanling Liu
    • , Jaime M Guidry Auvil
    • , Tanja M Davidsen
    • , Patee Gesuwan
    • , Leandro C Hermida
    • , Bodour Salhia
    • , Stephen Capone
    • , Giridharan Ramsingh
    • , Christian Michel Zwaan
    • , Sanne Noort
    • , Stephen R Piccolo
    • , E Anders Kolb
    • , Alan S Gamis
    • , Malcolm A Smith
    • , Daniela S Gerhard
    •  & Soheil Meshinchi
  • Article |

    ALOX12-mediated generation of 12-HETE leads to GPR31 activation and liver injury in ischemia–reperfusion, which can be targeted in a nonhuman primate model to improve outcome.

    • Xiao-Jing Zhang
    • , Xu Cheng
    • , Zhen-Zhen Yan
    • , Jing Fang
    • , Xiaozhan Wang
    • , Weijun Wang
    • , Zhen-Yu Liu
    • , Li-Jun Shen
    • , Peng Zhang
    • , Pi-Xiao Wang
    • , Rufang Liao
    • , Yan-Xiao Ji
    • , Jun-Yong Wang
    • , Song Tian
    • , Xue-Yong Zhu
    • , Yan Zhang
    • , Rui-Feng Tian
    • , Lin Wang
    • , Xin-Liang Ma
    • , Zan Huang
    • , Zhi-Gang She
    •  & Hongliang Li
  • Article |

    The deubiquitinase TNFAIP3 suppresses the kinase ASK1 to ameliorate nonalcoholic fatty liver disease.

    • Peng Zhang
    • , Pi-Xiao Wang
    • , Ling-Ping Zhao
    • , Xin Zhang
    • , Yan-Xiao Ji
    • , Xiao-Jing Zhang
    • , Chun Fang
    • , Yue-Xin Lu
    • , Xia Yang
    • , Mao-Mao Gao
    • , Yan Zhang
    • , Song Tian
    • , Xue-Yong Zhu
    • , Jun Gong
    • , Xin-Liang Ma
    • , Feng Li
    • , Zhihua Wang
    • , Zan Huang
    • , Zhi-Gang She
    •  & Hongliang Li
  • Correspondence |

    • Ross A Cardarelli
    • , Karen Jones
    • , Lucie I Pisella
    • , Heike J Wobst
    • , Lisa J McWilliams
    • , Paul M Sharpe
    • , Matthew P Burnham
    • , David J Baker
    • , Ilona Chudotvorova
    • , Justine Guyot
    • , Liliya Silayeva
    • , Danielle H Morrow
    • , Niek Dekker
    • , Stephen Zicha
    • , Paul A Davies
    • , Jörg Holenz
    • , Mark E Duggan
    • , John Dunlop
    • , Robert J Mather
    • , Qi Wang
    • , Igor Medina
    • , Nicholas J Brandon
    • , Tarek Z Deeb
    •  & Stephen J Moss
  • News & Views |

    In an article published recently in Nature Medicine, the authors generate organoid models of liver neoplasia. In doing so, they highlight both the diversity of current organoid methodologies and their application to cancer modeling and therapeutics discovery.

    • Amber R Smith
    •  & Calvin J Kuo
  • Corrigendum |

    • David Lagares
    • , Parisa Ghassemi-Kakroodi
    • , Caroline Tremblay
    • , Alba Santos
    • , Clemens K Probst
    • , Alicia Franklin
    • , Daniela M Santos
    • , Paula Grasberger
    • , Neil Ahluwalia
    • , Sydney B Montesi
    • , Barry S Shea
    • , Katharine E Black
    • , Rachel Knipe
    • , Meryem Blati
    • , Murray Baron
    • , Brian Wu
    • , Hassan Fahmi
    • , Rajiv Gandhi
    • , Annie Pardo
    • , Moisés Selman
    • , Jiangping Wu
    • , Jean-Pierre Pelletier
    • , Johanne Martel-Pelletier
    • , Andrew M Tager
    •  & Mohit Kapoor