A5065916368- Cancer Immunotherapy and Biomarkers
- Immunotherapy and Immune Responses
- CAR-T cell therapy research
- Immune Cell Function and Interaction
- Sphingolipid Metabolism and Signaling
- Histone Deacetylase Inhibitors Research
- Endoplasmic Reticulum Stress and Disease
- Glioma Diagnosis and Treatment
- Phagocytosis and Immune Regulation
- Lung Cancer Research Studies
- Microtubule and mitosis dynamics
- T-cell and B-cell Immunology
- Epigenetics and DNA Methylation
- Pharmacological Effects and Toxicity Studies
- Cancer Treatment and Pharmacology
Leiden University Medical Center
2025
The Netherlands Cancer Institute
2019-2024
Oncode Institute
2020-2024
University Medical Center Utrecht
2016-2021
Utrecht University
2021
Heidelberg University
2021
University Hospital Heidelberg
2021
Autotaxin (ATX; ENPP2) produces lysophosphatidic acid (LPA) that regulates multiple biological functions via cognate G protein-coupled receptors LPAR1-6. ATX/LPA promotes tumor cell migration and metastasis LPAR1 T motility LPAR2, yet its actions in the immune microenvironment remain unclear. Here, we show ATX secreted by melanoma cells is chemorepulsive for tumor-infiltrating lymphocytes (TILs) circulating CD8+ ex vivo, with functioning as an LPA-producing chaperone. Mechanistically,...
Radiotherapy (RT) is considered immunogenic, but clinical data demonstrating RT-induced T-cell priming are scarce. Here, we show in a mouse tumor model representative of human lymphocyte-depleted cancer that RT enhances spontaneous thymus-derived (FOXP3+ Helios+) regulatory T-cells (Tregs) by the tumor. These Tregs acquire an effector phenotype, populate and impede control simultaneous, CD8+ cytotoxic (CTL) response. Combination with CTLA-4 or PD-1 blockade, which enables CD28 costimulation,...
To increase cancer immunotherapy success, PD-1 blockade must be combined with rationally selected treatments. Here, we examined, in a poorly immunogenic mouse breast model, the potential of antibody-based immunomodulation and conventional anticancer treatments to collaborate anti-PD-1 treatment. One requirement improve anti-PD-1-mediated tumor control was promote tumor-specific cytotoxic T-cell (CTL) priming, which achieved by stimulating CD137 costimulatory receptor. A second overrule...
The antiepileptic drug valproic acid (VPA) inhibits histone deacetylase in glioblastoma cells vitro, which influences several oncogenic pathways and decreases glioma cell proliferation. clinical relevance of these observations remains unclear, as VPA does not seem to affect patient survival. In this study, we analyzed whether the vitro effects treatment on acetylation are also observed tumor tissues patients.The were assessed with immunofluorescence western blotting. On tissue microarrays...
T cell engineering strategies offer cures to patients and have entered clinical practice with chimeric antibody-based receptors; αβT receptor (αβTCR)-based are, however, lagging behind. To allow a more rapid successful translation concepts also using αβTCRs for engineering, incorporating method the purification of genetically modified cells, as well engineered deletion after transfer into patients, could be beneficial. This would increased efficacy, reduced potential side effects, improved...
Summary Autotaxin (ATX) is secreted by diverse cell types to produce lysophosphatidic acid (LPA) that regulates multiple biological functions via G protein-coupled receptors LPAR1-6. ATX/LPA promotes tumor migration and metastasis mainly LPAR1; however, its actions in the immune microenvironment remain unclear. Here, we show ATX melanoma cells chemorepulsive for tumor-infiltrating lymphocytes circulating CD8 + T ex vivo , with functioning as an LPA-producing chaperone. Mechanistically,...
Abstract To increase cancer immunotherapy success, PD-1 blockade must be combined with rationally selected treatments. Here, we examined in a poorly immunogenic mouse breast model the potential of antibody-based immunomodulation and conventional anti-cancer treatments to collaborate anti-PD-1 treatment. One important requirement improve anti-PD-1-mediated tumor control was promote tumor-specific cytotoxic T cell (CTL) priming, which achieved by stimulating CD137 costimulatory receptor. A...
Despite high expression of the angiogenic stimulator VEGF-A and recently reported autocrine VEGF-A-
<div>Abstract<p>To increase cancer immunotherapy success, PD-1 blockade must be combined with rationally selected treatments. Here, we examined, in a poorly immunogenic mouse breast model, the potential of antibody-based immunomodulation and conventional anticancer treatments to collaborate anti–PD-1 treatment. One requirement improve anti-PD-1–mediated tumor control was promote tumor-specific cytotoxic T-cell (CTL) priming, which achieved by stimulating CD137 costimulatory...
<div>Abstract<p>To increase cancer immunotherapy success, PD-1 blockade must be combined with rationally selected treatments. Here, we examined, in a poorly immunogenic mouse breast model, the potential of antibody-based immunomodulation and conventional anticancer treatments to collaborate anti–PD-1 treatment. One requirement improve anti-PD-1–mediated tumor control was promote tumor-specific cytotoxic T-cell (CTL) priming, which achieved by stimulating CD137 costimulatory...
<p>RNA sequencing data on day 8 after RIT of sorted cell populations from irradiated and non-irradiated AT-3 tumors.</p>
<p>Individual tumor size following radio-immunotherapy delivered as one dose or in 3 x 8 Gy fractions.</p>
<p>Identification of an AT-3 tumor-specific (CD8) T cell epitope, and targeting either Ly6G or CSF1R does not improve RIT-mediated control non-irradiated tumor.</p>
<p>Expression of the immunotherapy targets CD137 and PD-1 in AT-3 tumor-bearing mice.</p>
<p>Cisplatin modestly reduces the RIT-induced increase in CD8:CD4 T cell ratio and enhances (R)IT-medated control of non-irradiated tumors.</p>
<p>Depletion of effector phenotype T cells from the circulation following RIT combined with FTY720 treatment.</p>
<p>Expression of the immunotherapy targets CD137 and PD-1 in AT-3 tumor-bearing mice.</p>
<p>Individual tumor size following radio-immunotherapy delivered as one dose or in 3 x 8 Gy fractions.</p>
<p>Depletion of effector phenotype T cells from the circulation following RIT combined with FTY720 treatment.</p>
<p>Cisplatin modestly reduces the RIT-induced increase in CD8:CD4 T cell ratio and enhances (R)IT-medated control of non-irradiated tumors.</p>
<p>Identification of an AT-3 tumor-specific (CD8) T cell epitope, and targeting either Ly6G or CSF1R does not improve RIT-mediated control non-irradiated tumor.</p>
<p>RNA sequencing data on day 8 after RIT of sorted cell populations from irradiated and non-irradiated AT-3 tumors.</p>