Abstract A series of cancer vaccines have been evaluated in clinical trials with encouraging results, but the demonstration of clinical benefit in confirmatory studies has so far proven to be ...difficult. The development of cancer vaccines is hampered by a range of issues particular to this field of research. On 12th March 2008, the Biotherapy Development Association convened a workshop to discuss issues faced by scientists and clinicians involved in the development of cancer vaccines. This paper is a review of the field, based on discussions held at the BDA workshop, and describes biological barriers encountered in generating effective immune responses to tumours, methodological obstacles encountered in the improvement of immunological monitoring which aims to improve inter-laboratory and inter-trial comparisons, challenges in clinical trial design and problems posed by the lack of specific regulation for cancer vaccines and the impact on their development. Ultimately, a number of general solutions are posed: (1) better patient selection, (2) use of multi-modal treatments that affect several aspects of the immune system at once, (3) a requirement for the development of good biomarkers to stratify patients for selection prior to trial and as surrogates for clinical response and (4) harmonisation of SOPs for immunological monitoring of clinical trials.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Habitat manipulation through the incorporation of non-crop plants such as trap crops (to lure pests away from the cash crop) and insectary plants (to provide resources for natural enemies) into ...agro-ecosystems is an ecological approach to pest management. In a field-scale study, we quantified the effects of integrating the use of trap crops with insectary plants as a novel method to control pest herbivores in an organic cabbage agro-ecosystem. We hypothesized that pests would be concentrated in the trap crop habitat and suppressed by insectary-subsidized natural enemies in situ. We documented arthropod abundance (both adults and immature stages) associated with (1) two insectary plant species (sweet alyssum,
, and buckwheat,
) either alone or in combination; (2) a trap crop mixture of mighty mustard (
), red Russian kale (
var. acephala), and glossy collards (
var. italica), and (3) cabbage cash crop (
var. capitata). Trap crops were more attractive to pests than the cash crop. On a per-plant basis, densities of the herbivores
,
, and
were 154, 37, and 161× greater on the kale trap crop than on the cabbage cash crop, and 54, 18, and 89× greater on the collards trap crop than on the cash crop. Insectary plants contributed to the consumption of pests that aggregated on the trap crop. Parasitism of
by the braconid wasp
was significantly increased, and the abundance of eggs and larvae of the predatory coccinellid beetle
was greater on the trap crop in the presence of insectary plants compared to trap crops that lacked insectary plants. The 'Botanical Triad' of cash crop, trap crop, and insectary plants represents a new type of agro-ecosystem manipulation that integrates ecosystem service providers (e.g., predators and parasitoids) within the cropping system.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Classical ecological theory suggests that the coexistence of consumer species is fostered by resource-use differences, leading to greater resource use in communities with more species. However, ...explicit empirical support for this idea is lacking, because resource use by species is generally confounded with other species-specific attributes. We overcame this obstacle by co-opting behavioral plasticity in food choice among a group of animal consumers, allowing us to manipulate patterns of resource use while controlling for the effects of species identity and diversity. Within an aphid-parasitoid-radish community, we created a fully factorial manipulation of consumer resource-use breadth (specialist versus generalist) and species diversity (one versus three species) and found that resource exploitation improved with greater specialist, but not generalist, diversity. Therefore, resource partitioning, and not diversity per se, fostered greater overall resource consumption in our multispecies consumer communities.
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
We employed a combination of factorial experiments in the field and laboratory to investigate the relative magnitude and degree of interaction of bottom-up factors (two levels each of host-plant ...nutrition and vegetation complexity) and top-down forces (two levels of wolf-spider predation) on the population growth of Prokelisia planthoppers (P. dolus and P. marginata), the dominant insect herbivores on Spartina cordgrass throughout the intertidal marshes of North America. Treatments were designed to mimic combinations of plant characteristics and predator densities that occur naturally across habitats in the field. There were complex interactive effects between plant resources and spider predation on the population growth of planthoppers. The degree that spiders suppressed planthoppers depended on both plant nutrition and vegetation complexity, an interaction that was demonstrated both in the field and laboratory. Laboratory results showed that spiders checked planthopper populations most effectively on poor-quality Spartina with an associated matrix of thatch, all characteristics of high-marsh meadow habitats. It was also this combination of plant resources in concert with spiders that promoted the smallest populations of planthoppers in our field experiment. Planthopper populations were most likely to escape the suppressing effects of predation on nutritious plants without thatch, a combination of factors associated with observed planthopper outbreaks in low-marsh habitats in the field. Thus, there is important spatial variation in the relative strength of forces with bottom-up factors dominating under low-marsh conditions and top-down forces increasing in strength at higher elevations on the marsh. Enhancing host-plant biomass and nutrition did not strengthen top-down effects on planthoppers, even though nitrogen-rich plants supported higher densities of wolf spiders and other invertebrate predators in the field. Rather, planthopper populations, particularly those of Prokelisia marginata, escaped predator restraint on high-quality plants, a result we attribute to its mobile life history, enhanced colonizing ability, and rapid growth rate. Thus, our results for Prokelisia planthoppers suggest that the life history strategy of a species is an important mediator of top-down and bottom-up impacts. In laboratory mesocosms, enhancing plant biomass and nutrition resulted in increased spider reproduction, a cascading effect associated with planthopper increases on high-quality plants. Although the adverse effects of spider predation on planthoppers cascaded down and fostered increased plant biomass in laboratory mesocosms, this result did not occur in the field where top-down effects attenuated. We attributed this outcome in part to the intraguild predation of other planthopper predators by wolf spiders. Overall, the general paradigm in this system is for bottom-up forces to dominate, and when predators do exert a significant suppressing effect on planthoppers, their impact is generally legislated by vegetation characteristics.
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BFBNIB, FZAB, GIS, IJS, INZLJ, KILJ, NLZOH, NMLJ, NUK, OILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK, ZRSKP
Globally, grasslands have been heavily degraded, more so than any other biome. Grasslands of the eastern U.S. are no exception to this trend and, consequently, native biota associated with the ...region’s >20 million ha of agricultural grasslands are under considerable stress. For example, grassland associated breeding bird populations have declined precipitously in recent decades as have numerous species of pollinators. Although there is increasing awareness of the role grasslands can play in global carbon cycles and in providing high quality dietary proteins needed by an increasing global population, there is a lack of awareness of the alarming trends in the sustainability of the native biota of these ecosystems. Here, we present the status of this conservation challenge and offer prospective solutions through a working lands conservation approach. Such a strategy entails maintaining appropriate disturbances (i.e., grazing, fire, and their combination), improved grazing management, an increased reliance on native grasses and forbs, and improved plant diversity within pastures. Furthermore, we note some examples of opportunities to achieve these goals, offer suggestions for agricultural and conservation policy, and provide a framework for evaluating tradeoffs that are inevitably required when pursuing a multi-purpose grassland management framework.
Abstract Dendritic cell (DC) active immunotherapy is potentially efficacious in a broad array of malignant disease settings. However, challenges remain in optimizing DC-based therapy for maximum ...clinical efficacy within manufacturing processes that permit quality control and scale-up of consistent products. In this review we discuss the critical issues that must be addressed in order to optimize DC-based product design and manufacture, and highlight the DC based platforms currently addressing these issues. Variables in DC-based product design include the type of antigenic payload used, DC maturation steps and activation processes, and functional assays. Issues to consider in development include: (a) minimizing the invasiveness of patient biological material collection; (b) minimizing handling and manipulations of tissue at the clinical site; (c) centralized product manufacturing and standardized processing and capacity for commercial-scale production; (d) rapid product release turnaround time; (e) the ability to manufacture sufficient product from limited starting material; and (f) standardized release criteria for DC phenotype and function. Improvements in the design and manufacture of DC products have resulted in a handful of promising leads currently in clinical development.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
A vast body of research demonstrates that many ecological and evolutionary processes can only be understood from a tri‐trophic viewpoint, that is, one that moves beyond the pairwise interactions of ...neighbouring trophic levels to consider the emergent features of interactions among multiple trophic levels. Despite its unifying potential, tri‐trophic research has been fragmented, following two distinct paths. One has focused on the population biology and evolutionary ecology of simple food chains of interacting species. The other has focused on bottom‐up and top‐down controls over the distribution of biomass across trophic levels and other ecosystem‐level variables. Here, we propose pathways to bridge these two long‐standing perspectives. We argue that an expanded theory of tri‐trophic interactions (TTIs) can unify our understanding of biological processes across scales and levels of organisation, ranging from species evolution and pairwise interactions to community structure and ecosystem function. To do so requires addressing how community structure and ecosystem function arise as emergent properties of component TTIs, and, in turn, how species traits and TTIs are shaped by the ecosystem processes and the abiotic environment in which they are embedded. We conclude that novel insights will come from applying tri‐trophic theory systematically across all levels of biological organisation.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
•Interaction webs include both direct and indirect effects.•Herbivores can indirectly suppress other herbivores by attracting shared natural enemies.•Natural enemies can indirectly benefit plant ...yield without eating herbivores.•Mutualisms increase the frequency of indirect effects in insect communities.•Interaction webs reveal more opportunities to manipulate interactions to enhance yield.
Studies of insect communities in agroecosystems have historically focused on a food web approach: who eats whom. Recent research has highlighted the importance of indirect effects in determining the abundance and distribution of insects and their effects on other insects and plants. These indirect interactions include apparent competition where an herbivore indirectly suppresses another herbivore by attracting shared predators, cases where predators or even other herbivores alter the behavior and/or physiology of herbivores in ways that result in decreased plant consumption, and mutualisms that can generate a network of indirect effects that alter the abundance of many species within a community. The consequences of these indirect interactions have been modeled and proof-of-concept studies have demonstrated their potential importance, but studies of the consequences of these interactions on crop yield are sorely needed. Documenting the prevalence and consequences of these indirect effects in multiple crops will allow researchers to compare and contrast responses across systems and identify key species or characteristics of agroecosystems that dictate when and where these effects are important. This research will ultimately allow growers to manipulate these interactions to increase ecosystem services provided by insects and increase crop yield.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Drought threatens arthropod communities worldwide. Water limitation affects the quantity and quality of plants available to herbivores as food, and can also affect higher trophic-level consumers ...through variability in prey quality and reduced availability of suitable habitats. Our study assessed the response of an arthropod community to water limited wheat (
Triticum aestivum
L.) in a field setting. We used rainout shelters to exclude precipitation, irrigated raised bed plots to create three levels of water availability, and monitored arthropod community development over 8 weeks. First, we compared arthropod communities in habitats with different levels of water limitation and found that community composition was reliant on the magnitude of the water stress. This difference was largely due to the loss of piercing–sucking herbivores and predators in high-stress environments. Next, we focused on aphids and their natural enemies to investigate the underlying mechanisms driving community responses using structural equation modeling (SEM). Aphid abundance was negatively affected by water limitation, and this response was primarily associated with stress-induced plant physiological changes and not plant biomass or natural enemy abundance. Natural enemy abundance was also reduced in water-limited habitats, but natural enemies responded to plant biomass and not prey availability. These effects were exacerbated as water stress increased. The absence of natural enemy effects on aphids indicates that top–down predation effects were dampened by strong bottom–up effects of plant water limitation. This study revealed the importance of considering water stress intensity when predicting outcomes of droughts for arthropod communities.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Anecdotal data in the past have suggested that the effect of the western corn rootworm, Diabrotica virgifera virgifera LeConte (Coleoptera: Chrysomelidae), on maize yield is greater under drought and ...the effect of drought is greater under rootworm infestations, but no field experiments have controlled both moisture and rootworm levels. Field studies were conducted in 2012, 2013, and 2014 with treatments in a factorial arrangement of western corn rootworm infestation levels, and maize hybrids (with and without tolerance to drought and rootworm feeding). The experiment was repeated under well-watered and drought conditions in adjacent plots. Leaf water potential and stomatal conductance data suggested significant plant stress was achieved in the drought plots toward the end of the season each year and maize hybrids only played a minor role. In particular, in 2012 and 2013 yield was dramatically lower for the drought experiment than for the well-watered experiment. However, the impacts of rootworm infestation level and maize hybrids on water potential, stomatal conductance, and yield were variable across years and between experiments. In fact, the only year that the main effect of rootworm infestation levels significantly impacted yield was in 2014, when an extremely high infestation level was added and this was only for the well-watered portion of the experiment. Overall, rootworm infestation level played a relatively minor role in maize productivity and it did not appear that soil moisture level influenced that to a large degree.
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