Microglial cells are unique tissue-resident macrophages located in the parenchyma of the central nervous system (CNS). A recent comparative transcriptional study on microglia across more than 20 species from leach across chicken and many more up to humans revealed multiple conserved features. The results indicate the imperative role of microglia over the last 500 million years (Geirsdottir et al.
View Article and Find Full Text PDFCombination of radiation therapy (RT) with immune checkpoint blockade can enhance systemic anti-tumor T cell responses. Here, using two mouse tumor models, we demonstrate that adding long-acting CD122-directed IL-2 complexes (IL-2c) to RT/anti-PD1 further increases tumor-specific CD8 T cell numbers. The highest increase (>50-fold) is found in the blood circulation.
View Article and Find Full Text PDFPurpose: There is growing interest in combinations of immunogenic radiotherapy (RT) and immune checkpoint blockade, but clinical responses are still limited. Therefore, we tested the triple therapy with an inhibitor of the indoleamine 2,3-dioxygenase pathway, which like immune checkpoints, downregulates the antitumor immune response.
Experimental Design: Triple treatment with hypofractionated RT (hRT) + anti-PD-1 antibody (αPD1) + indoximod was compared with the respective mono- and dual therapies in two syngeneic mouse models.
Purpose: Localized radiotherapy can cause T-cell-mediated abscopal effects on nonirradiated metastases, particularly in combination with immune checkpoint blockade (ICB). However, results of prospective clinical trials have not met the expectations. We therefore investigated whether additional chemotherapy can enhance radiotherapy-induced abscopal effects in conjunction with ICB.
View Article and Find Full Text PDFInvasion of erythrocytes by merozoites is a composite process involving the interplay of several proteins. Among them, the Cysteine-Rich Protective Antigen (PfCyRPA) is a crucial component of a ternary complex, including Reticulocyte binding-like Homologous protein 5 (PfRH5) and the RH5-interacting protein (PfRipr), essential for erythrocyte invasion. Here, we present the crystal structures of PfCyRPA and its complex with the antigen-binding fragment of a parasite growth inhibitory antibody.
View Article and Find Full Text PDFThe identification of blood-borne biomarkers correlating with melanoma patient survival remains elusive. Novel techniques such as mass cytometry could help to identify melanoma biomarkers, allowing simultaneous detection of up to 100 parameters. However, the evaluation of multiparametric data generated via time-of-flight mass cytometry requires novel analytical techniques because the application of conventional gating strategies currently used in polychromatic flow cytometry is not feasible.
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