Increased Resistance of Bt Aspens to Phratora vitellinae (Coleoptera) Leads to Increased Plant Growth under Experimental Conditions

One main aim with genetic modification (GM) of trees is to produce plants that are resistant to various types of pests. The effectiveness of GM-introduced toxins against specific pest species on trees has been shown in the laboratory. However, few attempts have been made to determine if the production of these toxins and reduced herbivory will translate into increased tree productivity. We established an experiment with two lines of potted aspens (Populus tremula×Populus tremuloides) which express Bt (Bacillus thuringiensis) toxins and the isogenic wildtype (Wt) in the lab. The goal was to explore how experimentally controlled levels of a targeted leaf beetle Phratora vitellinae (Coleoptera; Chrysomelidae) influenced leaf damage severity, leaf beetle performance and the growth of aspen. Four patterns emerged. Firstly, we found clear evidence that Bt toxins reduce leaf damage. The damage on the Bt lines was significantly lower than for the Wt line in high and low herbivory treatment, respectively. Secondly, Bt toxins had a significant negative effect on leaf beetle survival. Thirdly, the significant decrease in height of the Wt line with increasing herbivory and the relative increase in height of one of the Bt lines compared with the Wt line in the presence of herbivores suggest that this also might translate into increased biomass production of Bt trees. This realized benefit was context-dependent and is likely to be manifested only if herbivore pressure is sufficiently high. However, these herbivore induced patterns did not translate into significant affect on biomass, instead one Bt line overall produced less biomass than the Wt. Fourthly, compiled results suggest that the growth reduction in one Bt line as indicated here is likely due to events in the transformation process and that a hypothesized cost of producing Bt toxins is of subordinate significance

Strategies to Target Tumor Immunosuppression

The tumor microenvironment is currently in the spotlight of cancer immunology research as a key factor impacting tumor development and progression. While antigen-specific immune responses play a crucial role in tumor rejection, the tumor hampers these immune responses by creating an immunosuppressive microenvironment. Recently, major progress has been achieved in the field of cancer immunotherapy, and several groundbreaking clinical trials demonstrated the potency of such therapeutic interventions in patients. Yet, the responses greatly vary among individuals. This calls for the rational design of more efficacious cancer immunotherapeutic interventions that take into consideration the “immune signature” of the tumor. Multimodality treatment regimens that aim to enhance intratumoral homing and activation of antigen-specific immune effector cells, while simultaneously targeting tumor immunosuppression, are pivotal for potent antitumor immunity

Macrophage metabolism controls blood vessel morphogenesis and metastasis

Tumor-associated macrophages (TAMs) display different phenotypes and specific metabolic fingerprints. Yet, whether and how metabolism influences TAM functions remains unknown. We report that REDD1, a negative regulator of the energy/nutrient sensor mTOR, is greatly induced in hypoxic TAMs. mTOR inhibition by REDD1 sustains the angiogenic capacity of TAMs, contributing to the formation of aberrant blood vessels. Genetic deletion of REDD1 leads to the formation of smoothly aligned, pericyte-covered blood vessels, which prevents hypoxia and metastasis in several tumor models. Molecularly, REDD1 inactivation unleashes mTOR in hypoxic TAMs thus enhancing glycolysis and NADH production, hence feeding a burst of mitochondrial ROS. ROS signaling stabilizes NF-κB that drives an angiostatic TAM phenotype, partly through the augmented production of the peptidase-inhibitor bectenecin. Systemic mTOR inhibition also promotes vessel abnormalization and metastasis, mostly due to its effect on TAMs. Our data provide a mechanism whereby TAM metabolism in hypoxia governs vascular remodeling and metastasis.nrpages: 114status: publishe

Sparks Fly in PGE2-Modulated Macrophage Polarization.

How macrophages convey extracellular signals by bridging metabolism and functions remains unclear. In this issue of Immunity, Sanin et al. (2018) report that prostaglandin E2 (PGE2) treatment in interleukin-4-activated macrophages suppresses mitochondrial membrane potential to control voltage-regulated genes involved in proliferation and immune responses