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Volume 515 Issue 7528, 27 November 2014

A tumour cell (left) interacts with three T cells and a tumour-infiltrating immune cell. This issue of Nature features five papers reflecting the current intense interest in the targeting of immune checkpoints as cancer therapy, and detailed work on identifying patients likely to respond this therapeutic strategy. Specifically, blockade of the transmembrane protein PD-L1 or its cell-surface receptor PD-1, upregulated in many different cancers, has shown promise in preclinical experiments and now in clinical trials. Powles et al. report on a clinical phase 1 study in metastatic urothelial bladder cancer treated with the anti-PD-L1 antibody MPDL3280A (page 558), and Tumeh et al. (page 568) and Herbst et al. (page 563) examine how PD-L1/PD-1 blockade enhances therapeutic responses in metastatic melanoma and lung cancer, respectively. Yadav et al. (page 572) and Gubin et al. (page 577) demonstrate the role of mutant tumour antigens in forming ligands for T-cell responses activated by PD-L1/PD-1 inhibition. Cover: Allison Bruce

Editorial

  • The US–China emissions agreement raises hopes for international cooperation on a climate accord. But it does not go far enough. 

    Editorial

    Advertisement

  • A slowdown in new cases offers a chance for control efforts to get ahead of the epidemic.

    Special:

    Editorial
  • A crowdfunded lunar mission might seem like a long shot — but there is no harm in trying.

    Editorial
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World View

  • As numbers of published articles rise, the scholarly review system must adapt to avoid unmanageable burdens and slipping standards, says Martijn Arns.

    • Martijn Arns
    World View
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Research Highlights

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Social Selection

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Seven Days

  • The week in science: Money woes for wave-power firm, ITER gets new leader and Turkish astrophysicist heads to jail.

    Seven Days
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News

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News Feature

  • When a handful of authors were caught reviewing their own papers, it exposed weaknesses in modern publishing systems. Editors are trying to plug the holes.

    • Cat Ferguson
    • Adam Marcus
    • Ivan Oransky
    News Feature
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Comment

  • Build precision microscopes to map atoms, say Stephen J. Pennycook and Sergei V. Kalinin.

    • Stephen J. Pennycook
    • Sergei V. Kalinin
    Comment
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Books & Arts

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Correspondence

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Correction

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News & Views

  • A study of the El Niño phenomenon over the past 21,000 years suggests that El Niño responded in complex ways to a changing climate, with several competing factors playing a part in its varying strength. See Letter p.550

    • Josephine R. Brown
    News & Views
  • A newly discovered skull from the Cretaceous period belongs to a mammal that was big, strange and fast-moving. The fossil solves a long-standing mystery, and helps to resolve a controversy about mammalian evolution. See Article p.512

    • Anne Weil
    News & Views
  • Five papers extend the list of cancers that respond to therapies that restore antitumour immunity by blocking the PD-1 pathway, and characterize those patients who respond best. See Letters p.558, p.563, p.568, p.572 & p.577

    • Jedd D. Wolchok
    • Timothy A. Chan
    News & Views
  • A geometric measurement of the distance to a nearby galaxy implies a larger mass for its central black hole than previously calculated, and a consequent increase for most other masses of such black holes. See Letter p.528

    • Martin Elvis
    News & Views
  • An analysis of fruit-fly embryos reveals that receptor proteins of the Toll family direct the oriented cell rearrangements required for the elongation of the head-to-tail axis during development. See Article p.523

    • Ulrich Tepass
    News & Views
  • Are you wondering what to prepare for dinner tonight? Data analyses reveal that certain food choices greatly benefit both your health and the environment. But what to do with this evidence remains a challenge to society. See Article p.518

    • Elke Stehfest
    News & Views
  • During immune-cell development, potentially self-reactive T cells are eliminated. It emerges that recruitment of a co-receptor bound to the T-cell receptor by the enzyme Lck is the rate-limiting step in this negative selection.

    • Nicholas R. J. Gascoigne
    News & Views
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Review Article

  • Growing evidence points to belowground biota as a significant contributor to aboveground diversity and functioning as well as impacting eco-evolutionary responses to environmental change; this review explores such evidence and proposes further research directions.

    • Richard D. Bardgett
    • Wim H. van der Putten
    Review Article
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Article

  • The gondwanatherians were mammals known only from teeth and some jaw fragments that lived in the southern continents alongside dinosaurs; here the entire cranium of a bizarre and badger-sized fossil mammal from the Cretaceous of Madagascar shows that gondwanatherians were related to the better-known multituberculates, a long-lived and successful group of now-extinct rodent-like mammals.

    • David W. Krause
    • Simone Hoffmann
    • Haingoson Andriamialison
    Article
  • Body axis elongation from head to tail is essential for animal development, however, the spatial cues that direct cell rearrangements relative to the anterior–posterior axis were unknown; this Drosophila study of convergent extension reveals that three Toll family receptors, expressed in overlapping stripes, modulate the contractile properties of cells to generate the polarized cell rearrangements that lead to body axis elongation.

    • Adam C. Paré
    • Athea Vichas
    • Jennifer A. Zallen
    Article
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Letter

  • A distance measurement based on observations of the hot-dust emitting region of the active galaxy NGC 4151 yields a value of 19 megaparsecs, implying a 1.4-fold increase in the dynamical mass of the galaxy’s central black hole and a corresponding correction to emission line reverberation masses of black holes in other active galactic nuclei if calibrated against NGC 4151′s dynamical mass.

    • Sebastian F. Hönig
    • Darach Watson
    • Jens Hjorth
    Letter
  • X-ray and neutron scattering measurements and ab initio molecular dynamics calculations show that the transition from an insulating phase to a metallic phase in vanadium dioxide is driven primarily by the entropic effects of soft anharmonic lattice vibrations, or phonons, which stabilize the metallic phase.

    • John D. Budai
    • Jiawang Hong
    • Olivier Delaire
    Letter
  • A multilayer photonic structure is described that strongly reflects incident sunlight while emitting heat selectively through an atmospheric transparency window to outer space; this leads to passive cooling under direct sunlight of 5 degrees Celsius below ambient air temperature, which has potential applications in air-conditioning and energy efficiency.

    • Aaswath P. Raman
    • Marc Abou Anoma
    • Shanhui Fan

    Special:

    Letter
  • A simulation of the evolution of El Niño Southern Oscillation in the past 21,000 years in a state-of-the-art climate model shows the complex response mechanisms of El Niño to external climate forcings and poses further challenges to our understanding and projection of El Niño in the future.

    • Zhengyu Liu
    • Zhengyao Lu
    • K. M. Cobb
    Letter
  • Single-molecular-interaction-sequencing involves attaching DNA barcodes to proteins, assaying these barcoded proteins en masse in an aqueous solution, followed by immobilization in a polyacrylamide film and amplifying and analysing the barcoding DNAs—the method allows for precise protein quantification and simultaneous interrogation of molecular binding affinity and specificity.

    • Liangcai Gu
    • Chao Li
    • George M. Church
    Letter
  • The dynamics of T-cell responses are investigated in tumour tissue from patients with advanced melanoma who were treated with a PD-1-blocking monoclonal antibody, revealing that clinical efficacy of the treatment correlates with increased frequencies of pre-existing CD8+ T cells and PD-1 and PD-L1 expression.

    • Paul C. Tumeh
    • Christina L. Harview
    • Antoni Ribas
    Letter
  • A combination of genome-wide exome and transcriptome analysis, mass spectrometry and computational structural modelling are used here to identify immunogenic neo-antigens in two mouse tumour cancer cell lines; mice vaccinated with predicted immunogenic peptides yielded therapeutically useful cytotoxic T-lymphocyte responses.

    • Mahesh Yadav
    • Suchit Jhunjhunwala
    • Lélia Delamarre
    Letter
  • A carcinogen-induced mouse tumour model is used here to show that mutant tumour-specific antigens are targets for CD8+ T-cell responses, mediating tumour regression after checkpoint blockade immunotherapy, and that these antigens can be used effectively in therapeutic vaccines; this advance potentially opens the door to personalized cancer vaccines.

    • Matthew M. Gubin
    • Xiuli Zhang
    • Robert D. Schreiber
    Letter
  • The authors identify a specific histone variant as a memory-suppressor that is initially reduced in expression within the hippocampus during memory formation; as a memory is consolidated to the cortex, reduced histone association with specific plasticity genes is observed, promoting stabilization of the memory.

    • Iva B. Zovkic
    • Brynna S. Paulukaitis
    • J. David Sweatt
    Letter
  • The Arabidopsis thaliana floral repressor FLC is epigenetically silenced by prolonged cold in a process called vernalization and then is reactivated before the completion of seed development; a histone demethylase, ELF6, is now shown to be involved in reactivating FLC in reproductive tissues, allowing the resetting of FLC expression and thus the requirement for vernalization in each generation.

    • Pedro Crevillén
    • Hongchun Yang
    • Caroline Dean
    Letter
  • To prime reverse transcription of Moloney murine leukaemia virus, a transfer RNA molecule must bind two regions of the retroviral RNA, the primer binding site (PBS) and primer activation signal within the U5-PBS; here, the NMR structures of the U5-PBS RNA and tRNA primer are solved, with and without the retroviral nucleocapsid protein, which remodels these regions.

    • Sarah B. Miller
    • F. Zehra Yildiz
    • Victoria M. D’Souza
    Letter
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Feature

  • The field of materials science is working to broaden the range of people it attracts.

    • Leigh Krietsch Boerner
    Feature
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Futures

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Outlook

  • People with the inherited bleeding disorder haemophilia lack factors that cause the blood to clot. The disease affects thousands of people around the world and has even played a part in historic events. By Neil Savage.

    • Neil Savage
    Outlook
  • Repairing the faulty genes that cause haemophilia could ultimately cure the disease, but it will be a tough challenge.

    • Julie Gould
    Outlook
  • History explains why people with haemophilia, and their physicians, are cautious to believe that a cure is in sight, says Stephen Pemberton.

    • Stephen Pemberton
    Outlook
  • Pills made from lettuce leaves could help to prevent one of the most serious complications of haemophilia treatment.

    • Elie Dolgin
    Outlook
  • A promising therapy curtails clotting inhibitors rather than replacing proteins that promote blood clotting.

    • Cassandra Willyard
    Outlook
  • The hunt is on for ways to diagnose and treat the joint problems that are now the main chronic problem in haemophilia.

    • Katharine Gammon
    Outlook
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Nature Outlook

  • Hopes are rising rapidly for people with the bleeding disorder haemophilia. The advent of longer-lasting blood-clotting factors is making treatment less onerous, and — on the horizon — gene therapy offers a potential cure.

    Nature Outlook
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