Pharmacological depletion of macrophages in a genetic mouse model of pancreatic cancer markedly reduced metastasis formation and is associated with impaired angiogenesis and reduced CD4+CD25+ T cell levels. Pharmacological targeting of infiltrating macrophages represents a promising novel tool for antimetastatic therapeutic approaches.

For future buildings (nZEBs according to EPBD) efficient and cost-effective heating systems with a high share of renewable energy ar0e1 r1equired. Heat pumps (HP) are considered as one of the key technologies in the building sector. However, in particular in high-density housing areas, source exploitation is strongly limited. Accordingly, the market in Austria does not currently provide real alternatives to apartment gas or electric boilers. Split type HPs with low power can be made compact and cost effective and thus offer new possibilities. However, split type HPs represent a real alternative only if the acceptance for them can be improved by means of improved modularity, design, architectural attractive integration in the building envelope and reduced sound emissions. The goal of the Austrian FFG research project FitNeS is the development and optimization of modular split HPs with compact and silent façade-integrated outdoor units. The outstanding features of the concept are a modular design with a high degree of prefabrication and representing a visually and architectonically attractive, economic and sustainable solution for both new constructions and renovations. Different concepts of façade-integrated outdoor units will be developed and evaluated with regard to design, façade construction, accessibility (for maintenance), building physics, efficiency, etc. on the basis of the technical and non-technical boundary conditions.

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BackgroundTumour-associated macrophages (TAM) play an important role in mediating tumour progression. In pancreatic cancer, infiltrating macrophages have been identified not only in invasive tumours, but also in early preinvasive pancreatic intraepithelial neoplasias and are known to mediate tumour progression.MethodsWe aimed to study the impact of pharmacological macrophage depletion by liposomal clodronate in the genetic mouse model of pancreatic cancer (KPC mouse: LSL-KrasG12D/+;LSL-Trp53R172H/+;Pdx-1-Cre). KPC mice were treated with liposomal clodronate or control liposomes from week 8 to week 20. Tumour and metastasis formation as well as alterations in local and circulating immune cells and cytokines were analysed.ResultsTreatment with liposomal clodronate effectively reduced CD11b-positive macrophages both in the pancreas and other organs such as liver, lung and spleen. Tumour incidence and size was only slightly reduced. However, metastasis formation in the liver und lungs was markedly diminished after macrophage depletion. Reduced macrophage count was associated with significant alterations in circulating growth factors and mediators known to be secreted by macrophages and associated with angiogenesis, most prominently VEGF. Moreover, application of liposomal clodronate led to marked alterations in circulating immune cells, among them reduced regulatory T cells.ConclusionsPharmacological depletion of macrophages in a genetic mouse model of pancreatic cancer markedly reduced metastasis formation and is associated with modulated profile of both secreted mediators and regulatory T cells. Pharmacological modulation of infiltrating macrophages represents a promising avenue for antimetastatic therapeutic approaches.