Activation of myeloid and endothelial cells by CD40L gene therapy supports T-cell expansion and migration into the tumor microenvironment

CD40 is an interesting target in cancer immunotherapy due to its ability to stimulate T-helper 1 immunity via maturation of dendritic cells and to drive M2 to M1 macrophage differentiation. Pancreatic cancer has a high M2 content that has shown responsive to anti-CD40 agonist therapy and CD40 may thus be a suitable target for immune activation in these patients. In this study, a novel oncolytic adenovirus armed with a trimerized membrane-bound extracellular CD40L (TMZ-CD40L) was evaluated as a treatment of pancreatic cancer. Further, the CD40L mechanisms of action were elucidated in cancer models. The results demonstrated that the virus transferring TMZ-CD40L had oncolytic capacity in pancreatic cancer cells and could control tumor progression. TMZ-CD40L was a potent stimulator of human myeloid cells and T-cell responses. Further, CD40L-mediated stimulation increased tumor-infiltrating T cells in vivo, which may be due to a direct activation of endothelial cells to upregulate receptors for lymphocyte attachment and transmigration. In conclusion, CD40L-mediated gene therapy is an interesting concept for the treatment of tumors with high levels of M2 macrophages, such as pancreatic cancer, and an oncolytic virus as carrier of CD40L may further boost tumor killing and immune activation

Alternative Energy Sources and Energy Justice:Nuclear, Hydro and Wind

The imperative of climate change is driving significant investment in low-carbon technologies. Justice scholars need to be cognisant of emerging injustices that are inherent to alternative low-carbon energy sources. This chapter assesses the main justice implications for the three energy sources: nuclear, hydro and wind. It spans the range of low-carbon technologies from the leading large-scale options in the form of nuclear and hydro as well as the more modern micro-solutions in wind energy. It includes an examination of resource availability including production and security concerns, accessibility in relation to consumption patterns and trade flows as well as broader sustainability questions. The energy justice framework is then applied to each low-carbon source in a similar manner to the previous chapte