76 research outputs found

    Tumor-derived GDF-15 blocks LFA-1 dependent T cell recruitment and suppresses responses to anti-PD-1 treatment

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    Immune checkpoint blockade therapy is beneficial and even curative for some cancer patients. However, the majority don’t respond to immune therapy. Across different tumor types, pre-existing T cell infiltrates predict response to checkpoint-based immunotherapy. Based on in vitro pharmacological studies, mouse models and analyses of human melanoma patients, we show that the cytokine GDF-15 impairs LFA-1/β2-integrin-mediated adhesion of T cells to activated endothelial cells, which is a pre-requisite of T cell extravasation. In melanoma patients, GDF-15 serum levels strongly correlate with failure of PD-1-based immune checkpoint blockade therapy. Neutralization of GDF-15 improves both T cell trafficking and therapy efficiency in murine tumor models. Thus GDF-15, beside its known role in cancer-related anorexia and cachexia, emerges as a regulator of T cell extravasation into the tumor microenvironment, which provides an even stronger rationale for therapeutic anti-GDF-15 antibody development. Experimental cancer immunology and therap

    Arthropod venom Hyaluronidases: biochemical properties and potential applications in medicine and biotechnology

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    39.4: Invited Paper:

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    Nanostructured polymer brushes and protein density gradients on diamond by carbon templating

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    Micro- and nanostructured polymer brushes on diamond can be directly prepared by carbon templating and amplification of the latent structures by photografting of a broad variety of vinyl monomers such as styrenes, acrylates and methacrylates. Even template structures with lateral dimensions as small as 5 nm can be selectively amplified and defined polymer brush gradients of a variety of functional polymers are realizable by this technique. Furthermore, conjugation with a model protein (GFP) results in protein density gradients of high loading and improved chemical stability. The effective functionalization of chemically and biologically inert diamond surfaces with stable functional polymer brushes, the possibility of structuring by the carbon templating technique and the direct biofunctionalization are crucial steps for the development of diamond based biosensors
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