Search

Current immunotherapies for lung cancer are only effective in a subset of patients. Identifying tumor-derived factors that facilitate immunosuppression offers the opportunity to develop novel strategies to supplement and improve current therapeutics. We sought to determine whether expression of driver oncogenes in lung cancer cells affects cytokine secretion, alters the local immune environment, and influences lung tumor progression. We demonstrate that oncogenic EGFR and KRAS mutations, which are early events in lung tumourigenesis, can drive cytokine and chemokine production by cancer cells. One of the most prominent changes was in CCL5, which was rapidly induced by KRASG12V or EGFRL858R expression, through MAPK activation. Immunocompetent mice implanted with syngeneic KRAS-mutant lung cancer cells deficient in CCL5 have decreased regulatory T cells (Tregs), evidence of T cell exhaustion, and reduced lung tumor burden, indicating tumor-cell CCL5 production contributes to an immune suppressive environment in the lungs. Furthermore, high CCL5 expression correlates with poor prognosis, immunosuppressive regulatory T cells, and alteration to CD8 effector function in lung adenocarcinoma patients. Our data support targeting CCL5 or CCL5 receptors on immune suppressive cells to prevent formation of an immune suppressive tumor microenvironment that promotes lung cancer progression and immunotherapy insensitivity.

The photophysical and chiroptical properties of a novel, chiral helicene‐NHC−Re(I) complex bearing an N‐(aza[6]helicenyl)‐benzimidazolylidene ligand are described, showing its ability to emit yellow circularly polarized luminescence. A comparative analysis of this new system with other helicene‐Re(I) complexes reported to date illustrates the impact of structural modifications on the emissive and absorptive properties. [ABSTRACT FROM AUTHOR]

Flexibility and innovation at creating shapes, adapting processes, and modifying materials characterize composites materials, a “high-tech” industry. However, the absence of standard manufacturing processes and the selection of materials with defined properties hinder the configuration of the composites materials supply chain. An interesting alternative for a “high-tech” industry such as composite materials would be to review supply chain lessons and practices in “low-tech” industries such as food. The main motivation of this study is to identify lessons and practices that comprise innovations in the supply chain of a firm in a perceived “low-tech” industry that can be used to provide guidelines in the design of the supply chain of a “high-tech” industry, in this case composite materials. This work uses the case study/site visit with analogy methodology to collect data from a Spanish leading producer of fresh fruit juice which is sold in major European markets and makes use of a cold chain. The study highlights supply base management and visibility/traceability as two elements of the supply chain in a “low-tech” industry that can provide guidelines that can be used in the configuration of the supply chain of the composite materials industry.

Norfolk Ridge bounds the northeastern edge of the continent of Zealandia and is proximal to where Cenozoic Tonga‐Kermadec subduction initiation occurred. We present and analyze new seismic reflection, bathymetric and rock data from Norfolk Ridge that show it is composed of a thick sedimentary succession and that it was formed and acquired its present‐day ridge physiography and architecture during Eocene to Oligocene uplift, emergence and erosion. Contemporaneous subsidence of the adjacent New Caledonia Trough shaped the western slope of Norfolk Ridge and was accompanied by volcanism. Neogene extension along the eastern slope of Norfolk Ridge led to the opening of the Norfolk Basin. Our observations reveal little or no contractional deformation, in contrast to observations elsewhere in Zealandia, and are hence significant for understanding the mechanics of subduction initiation. We suggest that subduction nucleated north of Norfolk Ridge and propagated rapidly along the ridge during the period 40‐35 Ma, giving it a linear and narrow shape. Slab roll‐back following subduction initiation may have preserved the ridge and created its eastern flank. Our observations suggest that pre‐existing structures, which were likely inherited from Cretaceous Gondwana subduction, were well‐oriented to propagate rupture and create self‐sustaining subduction. Plain Language Summary: Plate tectonic theory established and proved that the surface of Earth is composed of rigid moving plates, but it remains unclear how and why these plates sometimes re‐configure their boundaries and motions. Subduction zones are places where two plates converge and one plunges deep into the Earth beneath the other one. As the plate sinks, it drags the rest of the plate with it and acts as an engine that "pulls" the plate and drives horizontal motion. This is what drives the dynamics of plate tectonics. How are subduction zones created? This remains an open question, but we know from geological observations that new subduction zones do get created: more than half of all active subduction zones were created after the dinosaurs died out 65 million years ago. We present new observations from northern Zealandia (a submerged continent between New Zealand and New Caledonia) that document how one of the largest subduction zones on Earth, the Tonga‐Kermadec system, started. Key Points: We present new marine geophysical and geological data of Norfolk Ridge located along the northeastern edge of the Zealandia continentWe show that the ridge is not inherited from Cretaceous rifting that led to isolation of Zealandia but from the TECTA Cenozoic tectonic eventAnalysis of the structure and evolution of Norfolk Ridge underpins our understanding of tectonic processes of subduction initiation [ABSTRACT FROM AUTHOR]

The 2015 VESPA voyage (Volcanic Evolution of South Pacific Arcs) was a seismic and rock dredging expedition to the Loyalty and Three Kings Ridges and South Fiji Basin. In this paper we present 33 40Ar/39Ar, 22 micropaleontological, and two U/Pb ages for igneous and sedimentary rocks from 33 dredge sites in this little‐studied part of the southwest Pacific Ocean. Igneous rocks include basalts, dolerites, basaltic andesites, trachyandesites, and a granite. Successful Ar/Ar dating of altered and/or low‐K basalts was achieved through careful sample selection and processing, detailed petrographic and element mapping of groundmass, and incremental heating experiments on both phenocryst and groundmass separates to interpret the complex spectra produced by samples having multiple K reservoirs. The 40Ar/39Ar ages of most of the sampled lavas, irrespective of composition, are latest Oligocene to earliest Miocene (25–22 Ma); two are Eocene (39–36 Ma). The granite has a U/Pb zircon age of 23.6 ± 0.3 Ma. 40Ar/39Ar lava ages are corroborated by microfossil ages from associated sedimentary rocks. The VESPA lavas are part of a >3,000 km long disrupted belt of Eocene to Miocene subduction‐related volcanic rocks. The belt includes arc rocks in Northland New Zealand, Northland Plateau, Three Kings Ridge, and Loyalty Ridge and, speculatively, D'Entrecasteaux Ridge. This belt is the product of superimposed Eocene and Oligocene‐Miocene remnant volcanic arcs that were stranded along and near the edge of Zealandia while still‐active arc belts migrated east with the Pacific trench. Plain Language Summary: Samples of lava from the seabed between New Zealand and New Caledonia have been dated using atomic clocks and fossils. Most lavas erupted in a big pulse of volcanic activity between 25 and 22 million years ago. They are part of a belt of now‐extinct undersea volcanoes that stretches for more than 3,000 km between New Zealand and the Solomon Islands. These volcanoes were formed by subduction of the Pacific Plate under the Australian Plate. Key Points: A major pulse of 25–22 Ma volcanism is documented on the Loyalty and Three Kings Ridges, southwest Pacific OceanThe ridges are part of a more than 3,000 km long belt of Eocene to Miocene remnant volcanic arcs, stranded along the edge of ZealandiaWith care in sample selection, and petrological work, meaningful Ar/Ar ages can be obtained from altered and/or very low‐K submarine basalts [ABSTRACT FROM AUTHOR]