Publications by Freddy Radtke | EPFL Graph Search

Splenic fibroblasts control marginal zone B cell movement and function via two distinct Notch2-dependent regulatory programs

Innate-like splenic marginal zone (MZ) B (MZB) cells play unique roles in immunity due to their rapid responsiveness to blood-borne microbes. How MZB cells integrate cell-extrinsic and -intrinsic processes to achieve accelerated responsiveness is unclear. ...

2025

Early Notch signals from fibroblastic reticular cells program effector CD8+ T cell differentiation

Freddy Radtke, Ute Koch

A better understanding of the mechanisms regulating CD8+ T cell differentiation is essential to develop new strategies to fight infections and cancer. Using genetic mouse models and blocking antibodies, we uncovered cellular and molecular mechanisms by whi ...

ROCKEFELLER UNIV PRESS2025

Reciprocal inhibition of NOTCH and SOX2 shapes tumor cell plasticity and therapeutic escape in triple-negative breast cancer

Freddy Radtke, Nadine Fournier

Cancer cell plasticity contributes significantly to the failure of chemo- and targeted therapies in triple-negative breast cancer (TNBC). Molecular mechanisms of therapy-induced tumor cell plasticity and associated resistance are largely unknown. Using a g ...

2024

Bcl-xL targeting eliminates ageing tumor-promoting neutrophils and inhibits lung tumor growth

Freddy Radtke, Nadine Fournier, Etienne Meylan, Justine Pascual, Anita Bodac, Amber Dawn Bowler, Vincent Roh

Elevated peripheral blood and tumor-infiltrating neutrophils are often associated with a poor patient prognosis. However, therapeutic strategies to target these cells are difficult to implement due to the life-threatening risk of neutropenia. In a genetica ...

Springernature2024

Spatiotemporally resolved colorectal oncogenesis in mini-colons ex vivo

Matthias Lütolf, Freddy Radtke, Tania Hübscher, Amber Dawn Bowler, Nicolas Antoine Vincent Broguiere, Luis Francisco Lorenzo Martin

Three-dimensional organoid culture technologies have revolutionized cancer research by allowing for more realistic and scalable reproductions of both tumour and microenvironmental structures 1-3 . This has enabled better modelling of low-complexity cancer ...

NATURE PORTFOLIO2024

Disruption of stem cell niche-confined R-spondin 3 expression leads to impaired hematopoiesis

Freddy Radtke, Ute Koch, Jialin Zhang, Soufiane Boumahdi

Self-renewal and differentiation of stem and progenitor cells are tightly regulated to ensure tissue homeostasis. This regulation is enabled both remotely by systemic circulating cues, such as cytokines and hormones, and locally by various niche-confined f ...

ELSEVIER2023

Notch1 signaling is limited in healthy mature kidneys in vivo

Freddy Radtke

ObjectiveA Delta-Notch signaling component, Notch1, is involved in the normal development and multiple disorders of the kidney. Although the increase in Notch1 signaling is crucial to these pathogeneses, the basal signaling level in 'healthy' mature kidney ...

SPRINGERNATURE2023

Resistance mechanism to Notch inhibition and combination therapy in human T-cell acute lymphoblastic leukemia

Freddy Radtke, Nadine Fournier, Florence Armand, Romain Hamelin, Linlin Cao, Maria Pavlou

Gain-of-function mutations in NOTCH1 are among the most frequent genetic alterations in T-cell acute lymphoblastic leukemia (T-ALL), highlighting the Notch signaling pathway as a promising therapeutic target for personalized medicine. Yet, a major limitati ...

2023

Stroma-Driven Notch2 Signaling Controls Naive B Cell Fate By Regulating Microenvironmental Positioning within the Spleen

Freddy Radtke, Ute Koch

Amer Soc Hematology2023

Unraveling proteoglycofili: a potential new neutrophil defense mechanism

Freddy Radtke, Amber Dawn Bowler

Hoboken2023

Stromal Notch ligands foster lymphopenia-driven functional plasticity and homeostatic proliferation of naive B cells

Freddy Radtke, Ute Koch

In lymphopenic environments, secondary lymphoid organs regulate the size of B and T cell compartments by supporting the homeostatic proliferation of mature lymphocytes. The molecular mechanisms underlying these responses and their functional consequences r ...

AMER SOC CLINICAL INVESTIGATION INC2022

In vitro anti-lymphoma activity of the first-in-class pan-NOTCH transcription inhibitor CB-103

Freddy Radtke, Rajwinder Lehal, Maximilien Murone, Andrea Rinaldi

WILEY2022

Tcf1 is essential for initiation of oncogenic Notch1-driven chromatin topology in T-ALL

Freddy Radtke, Ute Koch, Christelle Dubey, Nadine Fournier, Marianne Nkosi, Tara Kimberly Sugrue, Mateusz Waldemar Antoszewski, Giovanni Ciriello

NOTCH1 is a well-established lineage specifier for T cells and among the most frequently mutated genes throughout all subclasses of T cell acute lymphoblastic leukemia (T-ALL). How oncogenic NOTCH1 signaling launches a leukemia-prone chromatin landscape du ...

AMER SOC HEMATOLOGY2022

Generation of a Gal4-dependent gene recombination and illuminating mouse

Freddy Radtke

Cell labeling technologies, including the Cre/loxP system, are powerful tools in developmental biology. Although the conventional Cre/loxP system has been extensively used to label the expression of specific genes, it is less frequently used for labeling p ...

INT PRESS EDITING CENTRE INC2022

A leukemia-protective germline variant mediates chromatin module formation via transcription factor nucleation

Freddy Radtke, Ute Koch, Bart Deplancke, Riccardo Dainese, Julie Marie Russeil, Daniel Alpern, Vincent Roland Julien Gardeux, Maria Litovchenko, Gerard Llimos Aubach, Jörn Pezoldt, Judith Franziska Kribelbauer

Non-coding variants coordinate transcription factor (TF) binding and chromatin mark enrichment changes over regions spanning >100 kb. These molecularly coordinated regions are named "variable chromatin modules" (VCMs), providing a conceptual framework of h ...

Nature Portfolio2022

The E protein-TCF1 axis controls gamma delta T cell development and effector fate

Freddy Radtke

TCF1 plays a critical role in T lineage commitment and the development of alpha beta lineage T cells, but its role in gamma delta T cell development remains poorly understood. Here, we reveal a regulatory axis where T cell receptor (TCR) signaling controls ...

2021

Notch signaling promotes disease initiation and progression in murine chronic lymphocytic leukemia

Freddy Radtke, Jessica Sordet, Ute Koch, Nadine Fournier, Marianne Nkosi, Delphine Maude Tardivon, Mateusz Waldemar Antoszewski

NOTCH1 gain-of-function mutations are recurrent in B-cell chronic lymphocytic leukemia (B-CLL), where they are associated with accelerated disease progression and refractoriness to chemotherapy. The specific role of NOTCH1 in the development and progressio ...

AMER SOC HEMATOLOGY2021

Notch1 Deficiency Induces Tumor Cell Accumulation Inside the Bronchiolar Lumen and Increases TAZ Expression in an Autochthonous Kras (LSL-G12V) Driven Lung Cancer Mouse Model

Freddy Radtke

Purpose: Abrogation of Notch signaling, which is pivotal for lung development and pulmonary epithelial cell fate decisions was shown to be involved in the aggressiveness and the differentiation of lung carcinomas. Additionally, the transcription factors YA ...

FRONTIERS MEDIA SA2021

Canonical Notch signaling controls the early thymic epithelial progenitor cell state and emergence of the medullary epithelia lineage in fetal thymus development

Freddy Radtke, Ute Koch, Dong Liu

Thymus function depends on the epithelial compartment of the thymic stroma. Cortical thymic epithelial cells (cTECs) regulate T cell lineage commitment and positive selection, while medullary (m) TECs impose central tolerance on the T cell repertoire. Duri ...

2020

Neutrophils suppress tumor-infiltrating T cells in colon cancer via matrix metalloproteinase-mediated activation of TGF beta

Marc-Olivier Sauvain, Freddy Radtke, Mauro Delorenzi, Nadine Fournier, Markus Germann, George Coukos, Amber Dawn Bowler

High T-cell infiltration in colorectal cancer (CRC) correlates with a favorable disease outcome and immunotherapy response. This, however, is only observed in a small subset of CRC patients. A better understanding of the factors influencing tumor T-cell re ...

2020