Maximilian M. L. Knott

High 4E-BP1 expression associates with chromosome 8 gain and CDK4/6 sensitivity in Ewing sarcoma

Cornelius M. Funk, Anna C. Ehlers, Martin F. Orth, Karim Aljakouch et autres

Chromosome 8 (chr8) gains are common in cancer, but their contribution to tumor heterogeneity is largely unexplored. Ewing sarcoma (EwS) is defined by FET::ETS fusions with few other recurrent mutations to explain clinical diversity. In EwS, chr8 gains are the second most …

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cIAP1 inhibitor of apoptosis is a tumor suppressor in Ewing sarcoma

Florencia Cidre‐Aranaz, Florian H. Geyer, Tilman L. B. Hoelting, Tobias Faehling et autres

ABSTRACT Ewing sarcoma (EwS) is a highly aggressive pediatric malignancy driven by EWSR1::ETS fusion oncoproteins –primarily EWSR1::FLI1– which deregulate genes essential for differentiation, proliferation, and cell survival. To uncover key downstream targets of this fusion involved in cell differentiation, we combined transcriptomic …

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Dynamic control of Argonautes by a rapidly evolving immunological switch

Chee Kiang Ewe, Guy Teichman, Shir Weiss, Maximilian M. L. Knott et autres

Small RNAs (sRNAs), coupled with Argonaute proteins (AGOs), regulate diverse biological processes, including immunity against nucleic acid parasites. C. elegans possesses an expanded repertoire of at least 19 AGOs functioning in an intricate gene regulatory network (GRN). However, the regulation of AGOs …

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Dynamic oncogene activity metabolically reprograms the tryptophan– kynurenine–AHR axis driving immune evasion and tumor progression in Ewing sarcoma

Martha J. Carreño-Gonzalez, Kimberley M. Hanssen, Ahmed Sadik, Alessa Henneberg et autres

ABSTRACT The extent to which dynamic changes in oncogene activity shape cancer cell metabolism and drive disease progression remains poorly understood. Ewing sarcoma (EwS), driven by EWSR1::ETS fusion transcription factors, constitutes an ideal model to interrogate this question, as fluctuations in fusion …

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Innate Immune Activation Is a Strong Suppressor of CCL22 and Impedes Regulatory T Cell–Dendritic Cell Interaction

Ignazio Piseddu, Jan Gärtig, Stephan Eiber, Stefan Moder et autres

The chemokine CCL22 is constitutively expressed at high levels in lymphoid organs, where it controls immunity by promoting contacts between dendritic cells (DC) and regulatory T cells (Treg). However, its regulation and impact in the context of pattern recognition receptor (PRR) stimulation …

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Dynamic Control of Argonautes by a Rapidly Evolving Immunological Switch

Chee Kiang Ewe, Guy Teichman, Maximilian M. L. Knott, Sarit Anava et autres

Abstract Small RNAs, coupled with Argonuate proteins (AGOs), regulate diverse biological processes, including immunity against nucleic acid parasites. C. elegans possesses an expanded repertoire of at least 19 AGOs functioning in an intricate gene regulatory network. Despite their crucial roles, little is …

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Mural cell-derived chemokines provide a protective niche to safeguard vascular macrophages and limit chronic inflammation

Kami Pekayvaz, Christoph Gold, Parandis Hoseinpour, Anouk Engel et autres

Maladaptive, non-resolving inflammation contributes to chronic inflammatory diseases such as atherosclerosis. Because macrophages remove necrotic cells, defective macrophage programs can promote chronic inflammation with persistent tissue injury. Here, we investigated the mechanisms sustaining vascular macrophages. Intravital imaging revealed a spatiotemporal macrophage niche …

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TLR-mediated immune activation is a strong suppressor of the Treg-attracting chemokine CCL22

Jan Gärtig, Juliane Grün, Carolin Perleberg, Konstantin Schnell et autres

Abstract The immunoregulatory chemokine CCL22 is mainly secreted by dendritic cells (DC) in lymph nodes and plays a crucial role in maintaining the balance between immune tolerance and efficient immune response by induction of intercellular contacts between DC and regulatory T cells …

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Transgenerational inheritance of engineered cytosine methylation in mice

Maximilian M. L. Knott, Oded Rechavi

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Data from Suppression of Intratumoral CCL22 by Type I Interferon Inhibits Migration of Regulatory T Cells and Blocks Cancer Progression

David Anz, Moritz Rapp, Stephan Eiber, Viktor H. Koelzer et autres

Abstract The chemokine CCL22 is abundantly expressed in many types of cancer and is instrumental for intratumoral recruitment of regulatory T cells (Treg), an important subset of immunosuppressive and tumor-promoting lymphocytes. In this study, we offer evidence for a generalized strategy to …

Supplementary Figure 3 from Suppression of Intratumoral CCL22 by Type I Interferon Inhibits Migration of Regulatory T Cells and Blocks Cancer Progression

David Anz, Moritz Rapp, Stephan Eiber, Viktor H. Koelzer et autres

Supplementary Figure 3-Correlation (corr) of intratumoral FoxP3+ cells and CCL22 levels in CT26 tumors from untreated mice.

Supplementary Figure 4 from Suppression of Intratumoral CCL22 by Type I Interferon Inhibits Migration of Regulatory T Cells and Blocks Cancer Progression

David Anz, Moritz Rapp, Stephan Eiber, Viktor H. Koelzer et autres

Supplementary Figure 4-Inducible secretion of CCL22 by CT26-CCL22dox cells.