The ability of CD8 T lymphocytes to eliminate tumors is limited by their ability to engender an immunosuppressive microenvironment. Here we describe a subset of tumor-infiltrating CD8 T cells marked by high expression of the immunosuppressive ATP ecto-nucleotidase CD39. The frequency of CD39CD8 T cells increased with tumor growth but was absent in lymphoid organs. Tumor-infiltrating CD8 T cells with high CD39 expression exhibited features of exhaustion, such as reduced production of TNF and IL2 and expression of coinhibitory receptors. Exhausted CD39CD8 T cells from mice hydrolyzed extracellular ATP, confirming that CD39 is enzymatically active. Furthermore, exhausted CD39CD8 T cells inhibited IFNγ production by responder CD8 T cells. In specimens from breast cancer and melanoma patients, CD39CD8 T cells were present within tumors and invaded or metastatic lymph nodes, but were barely detectable within noninvaded lymph nodes and absent in peripheral blood. These cells exhibited an exhausted phenotype with impaired production of IFNγ, TNF, IL2, and high expression of coinhibitory receptors. Although T-cell receptor engagement was sufficient to induce CD39 on human CD8 T cells, exposure to IL6 and IL27 promoted CD39 expression on stimulated CD8 T cells from human or murine sources. Our findings show how the tumor microenvironment drives the acquisition of CD39 as an immune regulatory molecule on CD8 T cells, with implications for defining a biomarker of T-cell dysfunction and a target for immunotherapeutic intervention. The tumor microenvironment elicits a subset of functionally exhausted CD8 T cells by creating conditions that induce cell surface expression of CD39, an immunosuppressive molecule that can be therapeutically targeted to restore effector T-cell function. .
Electrochemical reduction of CO2 has been pointed out as an interesting strategy to convert CO2 into useful chemicals. In addition, coupling CO2 electroreduction with renewable energies would allow storing electricity from intermittent renewable sources such as wind or solar power. In this work, an easy and fast method is adapted for the synthesis of pure and carbon supported Sn nanoparticles. The resulting nanoparticles have been characterized by transmission electron microscopy and their electrocatalytic properties towards CO2 reduction evaluated by cyclic voltammetry. Carbon supported Sn nanoparticles have been subsequently used to prepare Gas Diffusion Electrodes (Sn/C-GDEs). The electrodes have been characterized by scanning electron microscopy and also by cyclic voltammetry.
2Finally, the electrodes were tested on a continuous and single pass CO2 electroreduction filter-press type cell system in aqueous solution, to obtain formate at ambient pressure and temperature. These Sn/C-GDEs allow working at high current densities with low catholyte flow. Thus, for instance, at 150 mA cm -2 , a 70 % Faradaic Efficiency (FE) was obtained with a formate concentration of 2.5 g L -1 . Interestingly, by increasing the current density to 200 mA cm -2 and decreasing the flow rate, a concentration over 16 g L -1 was reached.Despite the high concentrations obtained, further research is still required to keep high FE operating at high current densities.
Electrochemical reduction has been pointed out as a promising method for CO 2 valorisation into useful chemicals. This paper studies the influence of key variables on the performance of an experimental system for continuous electro-reduction of CO 2 to formate, when a tin plate is used as working electrode. Particular emphasis is placed on comparing the performance of Sn and Pb as cathodes. As was previously found with Pb, the influence of current density ("j") using Sn was particularly noteworthy, and when j was raised up to a limit value of 8.5 mA cm-2 , important increases of the rate of formate production were observed at the expense of lowering the Faradaic efficiency. However, unlike what was found with Pb, the performance using Sn improved when the electrolyte flow rate/electrode area ratio was increased within the range studied (0.57-2.3 mL min-1 cm-2). In this way, the use of Sn as cathode allowed achieving rates of formate production that were 25% higher than the maximum rates obtained with Pb, together with Faradaic efficiencies close to 70%, which were 15 points higher than
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