An Antibody Targeting ICOS Increases Intratumoral Cytotoxic to Regulatory T-cell Ratio and Induces Tumor Regression.

The immunosuppressive tumor microenvironment constitutes a significant hurdle to immune checkpoint inhibitor responses. Both soluble factors and specialized immune cells, such as regulatory T cells (Treg), are key components of active intratumoral immunosuppression. Inducible costimulatory receptor (ICOS) can be highly expressed in the tumor microenvironment, especially on immunosuppressive Treg, suggesting that it represents a relevant target for preferential depletion of these cells. Here, we performed immune profiling of samples from tumor-bearing mice and patients with cancer to demonstrate differential expression of ICOS in immune T-cell subsets in different tissues. ICOS expression was higher on intratumoral Treg than on effector CD8 T cells. In addition, by immunizing an Icos knockout transgenic mouse line expressing antibodies with human variable domains, we selected a fully human IgG1 antibody called KY1044 that bound ICOS from different species. We showed that KY1044 induced sustained depletion of ICOShigh T cells but was also associated with increased secretion of proinflammatory cytokines from ICOSlow effector T cells (Teff). In syngeneic mouse tumor models, KY1044 depleted ICOShigh Treg and increased the intratumoral TEff:Treg ratio, resulting in increased secretion of IFNγ and TNFα by TEff cells. KY1044 demonstrated monotherapy antitumor efficacy and improved anti-PD-L1 efficacy. In summary, we demonstrated that using KY1044, one can exploit the differential expression of ICOS on T-cell subtypes to improve the intratumoral immune contexture and restore an antitumor immune response.

Annual estimates of occupancy for bryophytes, lichens and invertebrates in the UK, 1970-2015.

Here, we determine annual estimates of occupancy and species trends for 5,293 UK bryophytes, lichens, and invertebrates, providing national scale information on UK biodiversity change for 31 taxonomic groups for the time period 1970 to 2015. The dataset was produced through the application of a Bayesian occupancy modelling framework to species occurrence records supplied by 29 national recording schemes or societies (n = 24,118,549 records). In the UK, annual measures of species status from fine scale data (e.g. 1 × 1 km) had previously been limited to a few taxa for which structured monitoring data are available, mainly birds, butterflies, bats and a subset of moth species. By using an occupancy modelling framework designed for use with relatively low recording intensity data, we have been able to estimate species trends and generate annual estimates of occupancy for taxa where annual trend estimates and status were previously limited or unknown at this scale. These data broaden our knowledge of UK biodiversity and can be used to investigate variation in and drivers of biodiversity change.

Mass Seasonal Migrations of Hoverflies Provide Extensive Pollination and Crop Protection Services.

Despite the fact that migratory insects dominate aerial bioflows in terms of diversity, abundance, and biomass [1-6], the migration patterns of most species, and the effects of their annual fluxes between high- and low-latitude regions, are poorly known. One important group of long-range migrants that remain understudied is a suite of highly beneficial species of hoverfly in the tribe Syrphini, which we collectively term "migrant hoverflies." Adults are key pollinators [7-10] and larvae are significant biocontrol agents of aphid crop pests [11], and thus, it is important to quantify the scale of their migrations and the crucial ecosystem services they provide with respect to energy, nutrient, and biomass transport; regulation of crop pests; and pollen transfer. Such assessments cannot be made by sporadic observations of mass arrivals at ground level, because hoverflies largely migrate unnoticed high above ground. We used insect-monitoring radars [12] to show that up to 4 billion hoverflies (80 tons of biomass) travel high above southern Britain each year in seasonally adaptive directions. The long-range migrations redistribute tons of essential nutrients (nitrogen [N] and phosphorus [P]) and transport billions of pollen grains between Britain and Europe, and locally produced populations consume 6 trillion aphids and make billions of flower visits. Migrant hoverfly abundance fluctuated greatly between years, but there was no evidence of a population trend during the 10-year study period. Considering that many beneficial insects are seriously declining [7, 10, 13-19], our results demonstrate that migrant hoverflies are key to maintaining essential ecosystem services.

Developing and enhancing biodiversity monitoring programmes: a collaborative assessment of priorities.

Biodiversity is changing at unprecedented rates, and it is increasingly important that these changes are quantified through monitoring programmes. Previous recommendations for developing or enhancing these programmes focus either on the end goals, that is the intended use of the data, or on how these goals are achieved, for example through volunteer involvement in citizen science, but not both. These recommendations are rarely prioritized.We used a collaborative approach, involving 52 experts in biodiversity monitoring in the UK, to develop a list of attributes of relevance to any biodiversity monitoring programme and to order these attributes by their priority. We also ranked the attributes according to their importance in monitoring biodiversity in the UK. Experts involved included data users, funders, programme organizers and participants in data collection. They covered expertise in a wide range of taxa.We developed a final list of 25 attributes of biodiversity monitoring schemes, ordered from the most elemental (those essential for monitoring schemes; e.g. articulate the objectives and gain sufficient participants) to the most aspirational (e.g. electronic data capture in the field, reporting change annually). This ordered list is a practical framework which can be used to support the development of monitoring programmes.People's ranking of attributes revealed a difference between those who considered attributes with benefits to end users to be most important (e.g. people from governmental organizations) and those who considered attributes with greatest benefit to participants to be most important (e.g. people involved with volunteer biological recording schemes). This reveals a distinction between focussing on aims and the pragmatism in achieving those aims. Synthesis and applications. The ordered list of attributes developed in this study will assist in prioritizing resources to develop biodiversity monitoring programmes (including citizen science). The potential conflict between end users of data and participants in data collection that we discovered should be addressed by involving the diversity of stakeholders at all stages of programme development. This will maximize the chance of successfully achieving the goals of biodiversity monitoring programmes.