A5026022554- Acute Myeloid Leukemia Research
- Immune Cell Function and Interaction
- Immune cells in cancer
- Immunotherapy and Immune Responses
- CAR-T cell therapy research
- RNA Research and Splicing
- RNA modifications and cancer
- Hematological disorders and diagnostics
- RNA and protein synthesis mechanisms
- Viral Infections and Outbreaks Research
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Sarcoma Diagnosis and Treatment
- Protein Degradation and Inhibitors
- Bone and Joint Diseases
- Single-cell and spatial transcriptomics
- Multiple Myeloma Research and Treatments
- Burn Injury Management and Outcomes
- T-cell and B-cell Immunology
- Virus-based gene therapy research
- Ubiquitin and proteasome pathways
- Cancer Immunotherapy and Biomarkers
Erasmus MC - Sophia Children’s Hospital
2023-2025
Princess Máxima Center
2023-2025
University Medical Center Utrecht
2024-2025
University of Trento
2020-2021
Abstract While the introduction of T cell-based immunotherapies has improved outcomes in many cancer types, development for both adult and pediatric AML been relatively slow limited. In addition to need identify suitable target antigens, a better understanding immunosuppressive tumor microenvironment is necessary design novel immunotherapy approaches. To date, most immune characterization studies have focused on cells, while innate lineages such as monocytes, granulocytes natural killer (NK)...
Abstract Because of the low mutational burden and consequently, fewer potential neoantigens, children with acute myeloid leukemia (AML) are thought to have a T cell-depleted or ‘cold’ tumor microenvironment may likelihood response cell-directed immunotherapies. Understanding composition, phenotype, spatial organization cells other microenvironmental populations in pediatric AML bone marrow (BM) is essential for informing future immunotherapeutic trials about targetable immune-evasion...
Proteolysis targeting chimeras (PROTACs) are heterobifunctional small molecules that utilize the ubiquitin-proteasome system to selectively degrade target proteins. This innovative technology has shown remarkable efficacy and specificity in degrading oncogenic proteins progressed through various stages of preclinical clinical development for hematologic malignancies, including adult acute myeloid leukemia (AML). However, application PROTACs pediatric AML remains largely unexplored. In this...
A better understanding of lymphocyte dynamics during current treatment regimens in pediatric AML is urgently needed to understand whether the application bispecific T-cell-engagers (BiTEs) periods low tumor burden could be a viable strategy. In this study, we found that induction 1, comprising mitoxantrone-etoposide-cytarabine nearly all patients (as part NOPHO-DBH AML-2012 protocol), led preserved or increased relative abundances alongside marked blast reduction most cases. This was...
Abstract Background Medulloblastoma (MB) is one of the most prevalent paediatric brain malignancies and makes up ~20% all primary tumours in children. Current treatment options are not curative for approximately 30% patients leave survivors with an impaired quality life. Immune checkpoint inhibition can offer a novel targeted therapy but largely remains understudied MB. The aim this study was to determine whether dual immune be used as Methods We utilised single cell nuclei sequencing...
DHX30 was recently implicated in the translation control of mRNAs involved p53-dependent apoptosis. Here, we show that exhibits a more general function by integrating activities its cytoplasmic isoform and abundant mitochondrial one. The depletion both isoforms HCT116 cells leads to constitutive changes polysome-associated mRNAs, enhancing coding for ribosomal proteins while reducing translational efficiency nuclear-encoded mitoribosome mRNAs. Furthermore, higher global but slower...
Abstract Because of the low mutational burden and consequently, fewer potential neoantigens, children with acute myeloid leukemia (AML) are thought to have a T cell-depleted or ‘cold’ tumor microenvironment may likelihood response cell-directed immunotherapies. Understanding composition, phenotype, spatial organization cells other microenvironmental populations in pediatric AML bone marrow (BM) is essential for informing future immunotherapeutic trials about targetable immune-evasion...
Summary Immunotherapy has made significant advancements in cancer treatments, improving patients’ survival rates and quality of life. Several challenges still need to be addressed, which include the considerable fraction incomplete curative responses patients, development therapy resistance by tumours, occurrence adverse effects, such as inflammatory autoimmune complications. Paediatric tumours usually exhibit lower responsiveness immunotherapies compared adult tumours. Although underlying...
Abstract Medulloblastoma (MB) is one of the most prevalent pediatric brain malignancies and makes up approximately 20% all primary tumors in children. Current treatment options are not curative for about 30% patients leave survivors with an impaired quality life. Immune checkpoint inhibition can offer a novel targeted therapy but largely remains understudied MB. The aim this study was to determine whether immune be used as We MB cell lines, patient-derived xenograft (PDX) organoid models,...
Pediatric cancers are characterized by a relatively low mutational burden and therefore, children thought to be poor candidates for T cell-engaging immunotherapies. Here, we performed multidimensional characterization of the tumor immune microenvironment in newly diagnosed with acute myeloid leukemia (AML) non-leukemic controls. We identified subset pediatric AML patients remarkably high levels cell infiltration abundance anti-inflammatory macrophages bone marrow. In addition, detected large...
Background: Pediatric acute myeloid leukemia (AML) is a cancer with particularly low mutational burden in comparison to other pediatric and adult cancers therefore, thought be poor candidate for T cell-engaging immunotherapies. Interestingly, recent evidence suggests that considerable variation immune cell infiltration exists among immunologically ‘cold’ cancers, subsets of patients showing ‘hot’ tumor microenvironment improved responses immunotherapy their counterparts. However, little...
Abstract DHX30 was recently implicated in the translation control of mRNAs involved p53-dependent apoptosis. Here we show that exhibits a more general function by integrating activities its cytoplasmic isoform and abundant mitochondrial one. The depletion both isoforms HCT116 cells leads to constitutive changes polysome-associated mRNAs, enhancing coding for ribosomal proteins while reducing translational efficiency nuclear-encoded mitoribosome mRNAs. Furthermore, higher global but slower...