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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
The Public Library of Science’s open-data mandate has prompted scientists to share more data online, but not everyone is complying with the regulations.
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.
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
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
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
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
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
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
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.
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.
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.
As incomes grow, diets change, with varying impacts on human health and the environment; here the links are examined and suggestions made for diets that both improve health and minimize environmental impacts.
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.
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.
Analysis of data obtained by probe spacecraft shows that ultrarelativistic electrons in the Van Allen radiation belts are prevented from entering a sharply defined region around the Earth, possibly owing to a combination of slow natural inward diffusion and pitch angle scattering.
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.
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.
Flash memories are essential for modern electronics; here a selenium-templated polyoxometalate is used to engineer new metal–oxide–semiconductor devices.
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.
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.
The results of a clinical phase I study in metastatic urothelial bladder cancer treated with the MPDL3280A antibody show that expression of PD-L1 on tumour-infiltrating immune cells is relevant for the therapeutic response.
Clinical and correlative biomarker results from a phase 1 clinical trial in patients with different solid tumours are presented; the findings indicate that PD-L1 expression on tumour-infiltrating immune cells is associated with clinical response to MPDL3280A (anti-PD-L1).
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.
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.
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.
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.
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.
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.
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.
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.