A5016627657- Immunotherapy and Immune Responses
- CAR-T cell therapy research
- Cancer Immunotherapy and Biomarkers
- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Bladder and Urothelial Cancer Treatments
- Colorectal and Anal Carcinomas
- Cancer Risks and Factors
- Genetic factors in colorectal cancer
- Colorectal Cancer Treatments and Studies
- Monoclonal and Polyclonal Antibodies Research
- Inflammatory Biomarkers in Disease Prognosis
- RNA Interference and Gene Delivery
- Immune cells in cancer
- Virus-based gene therapy research
- Cancer Cells and Metastasis
- Cervical Cancer and HPV Research
- Colorectal Cancer Surgical Treatments
- Cytomegalovirus and herpesvirus research
- Reproductive System and Pregnancy
- vaccines and immunoinformatics approaches
- Cancer Genomics and Diagnostics
- RNA modifications and cancer
- Lymphoma Diagnosis and Treatment
- Nanoplatforms for cancer theranostics
The Netherlands Cancer Institute
2002-2024
Oncode Institute
1995-2024
Cancer Center Amsterdam
2012-2019
Vrije Universiteit Amsterdam
1998-2019
Amsterdam University Medical Centers
2019
Dutch Cancer Society
2019
Amsterdam UMC Location Vrije Universiteit Amsterdam
2008-2017
Vanderbilt University Medical Center
2015
University Medical Center
2013-2014
University Hospital and Clinics
2013-2014
Surgery for locoregionally advanced head and neck squamous cell carcinoma (HNSCC) results in 30‒50% five-year overall survival. In IMCISION (NCT03003637), a non-randomized phase Ib/IIa trial, 32 HNSCC patients are treated with 2 doses (in weeks 1 3) of immune checkpoint blockade (ICB) using nivolumab (NIVO MONO, n = 6, Ib arm A) or plus single dose ipilimumab (COMBO, 26, 6 B, 20 IIa) prior to surgery. Primary endpoints feasibility resect no later than week (phase Ib) primary tumor...
Notch signaling is known to differentially affect the development of lymphoid B and T cell lineages, but it remains unclear whether such effects are specifically dependent on distinct ligands. Using a coculture assay we observed that ligand Delta-1 completely inhibits differentiation human hematopoietic progenitors into lineage while promoting emergence cells with phenotype cell/natural killer (NK) precursors. In contrast, Jagged-1 did not disturb either or cell/NK development. Furthermore,...
To better understand the expression pattern of programmed death-ligand 1 (PD-L1) in different breast cancer types, we characterized PD-L1 tumor and tumor-infiltrating immune cells, relation to mutation rate, BRCA1-like status survival. We analyzed 410 primary treatment-naive tumors comprising 162 estrogen receptor-positive (ER+) HER2-, 101 HER2+ 147 triple-negative (TN) cancers. Pathologists quantified lymphocytes (TILs) cells TILs using whole slides tissue microarray. Mutation rate was...
Abstract The androgen receptor (AR) is the master regulator of prostate cancer (PCa) development, and inhibition AR signalling most effective PCa treatment. expressed in cells also PCa-associated stroma, including infiltrating macrophages. Macrophages have a decisive function initiation progression, but role macrophages remains largely unexplored. Here, we show that macrophage-like THP-1 cell line supports migration invasion culture via increased Triggering Receptor Expressed on Myeloid...
Patients with advanced penile squamous cell carcinoma have a poor prognosis (21% 2-year overall survival [OS] from diagnosis). We assessed the activity of atezolizumab (anti-PD-L1) in patients cancer, or without radiotherapy (RT).A single-center, nonrandomized phase II study two treatment arms was conducted 32 histologically confirmed cancer. All received (1,200 mg) once every 3 weeks. Twenty patients, who were expected to benefit RT for locoregional disease control, additional irradiation....
Abstract Replicative senescence of T cells is correlated with erosion telomere ends. Telomerase plays a key role in maintaining length. Therefore, it thought that telomerase regulates the life span cells. To test this hypothesis, we have over-expressed human reverse transcriptase CD8+ Ectopic expression led to immortalization these cells, without altering phenotype and loss specificity or functionality. As remained dependent on cytokines Ag stimulation for their vitro expansion, conclude was...
In this study we investigated whether the presence of specific populations tumor infiltrating lymphocytes (TILs) in diagnostic primary melanoma biopsies are related to outcome clinically stage II patients. Moreover, TILs correlates with expression MHC class I antigen and on cells and/or presenting cells. Diagnostic samples 15 patients an unfavorable were compared 20 favorable outcome. Patients matched for age, gender Breslow thickness. Biopsies examined granzyme B+, CD8+, CD4+ CD56+ A...
Intact cells of Saccharomyces cerevisiae were able to endocytose FITC-dextrans 70 kDa, but not 150 whereas spheroplasts took up both components. The rate uptake kDa dextrans by was about three times higher than that intact cells. Pretreatment with dithiothreitol (DTT) or EDTA increased the considerably, still excluded. Release periplasmic invertase activity into medium glucose-derepressed negligible in control cell suspensions, strongly stimulated presence DTT. released had an apparent...
Adoptive cell transfer of tumor infiltrating lymphocytes has shown clinical efficacy in the treatment melanoma and is now also being explored other types. Generation sufficient numbers effector T cells requires extensive ex vivo expansion, often at cost differentiation potency. For past 20 years, IL-2 been key cytokine applied expansion TIL for ACT. However, use led to collateral regulatory (Tregs) progressive differentiation, factors known limit persistence activity transferred TIL. The...
Though Vγ9Vδ2-T cells constitute only a small fraction of the total T cell population in human peripheral blood, they play vital role tumor defense and are therefore major interest to explore for cancer immunotherapy. cell-based immunotherapeutic approaches developed so far have been generally well tolerated were able induce significant clinical responses. However, overall results inconsistent, possibly due fact that these strategies induced systemic activation without preferential...
Abstract Immune checkpoint inhibitors (ICI) can achieve remarkable responses in urothelial cancer (UC), which may depend on tumor microenvironment (TME) characteristics. However, the relationship between TME, usually characterized by immune cell density, and response to ICI is unclear. Here, we quantify TME densities spatial relationships (SRs) of 24 baseline UC samples, obtained before pre-operative combination treatment, using multiplex immunofluorescence. We describe SRs approximating...
Abstract Monocyte infiltration into inflamed tissue requires their initial arrest onto the endothelial cells (ECs), followed by firm adhesion and subsequent transmigration. Although several pairs of molecules have been shown to play a role in monocytes ECs, mechanism transendothelial migration is poorly defined. In this study, we investigated signal-regulatory protein (SIRP)α-CD47 interactions monocyte transmigration across brain ECs. CD47 expression was observed vivo on cerebral endothelium...
Ewing sarcoma (EWS) is a tumour most commonly arising in bone, although on occasion soft tissue, with poor prognosis patients refractory or relapsed disease, despite multimodal therapy. Immunotherapeutic strategies based tumour-reactive T and/or natural killer cells may improve the treatment of advanced-stage EWS. Since cellular immune recognition critically depends human leukocyte antigen (HLA) expression, knowledge about HLA expression EWS crucial design immunotherapeutic strategies....
The human immunodeficiency virus type 1 (HIV-1)-specific CD8 cytotoxic T-lymphocyte (CTL) response plays a critical role in controlling HIV-1 replication. Augmenting this should enhance control of replication and stabilize or improve the clinical course disease. Although cytomegalovirus (CMV) Epstein-Barr (EBV) infection immunocompromised patients can be treated by adoptive transfer ex vivo-expanded CMV- EBV-specific CTLs, vivo-expanded, autologous HIV-1-specific CTLs had minimal effects on...
Active specific immunotherapy (ASI) consisting of an autologous tumor cell vaccine given as adjuvant treatment has been shown to improve recurrence-free survival patients with colon cancer. The aim the current retrospective study was investigate whether beneficial effects ASI correlated microsatellite instability (MSI), which is considered important biologic determinant cancer.Microsatellite status assessed on archival material from stage II and III Microsatellite next associated clinical...
Toll-like receptor (TLR) ligands are attractive candidate adjuvants for therapeutic cancer vaccines, since TLR signaling stimulates and tunes both humoral cellular immune responses induced by dendritic cells (DCs). Given that human skin contains a dense network of DCs, which easily accessible via (intra-)dermal delivery is actively explored as an antitumor vaccination site. Here we used explant model to explore the potential DC activation in their complex microenvironment. We show topical...
Microsatellite instability (MSI) has been associated with favourable survival in early stage colorectal cancer (CRC) compared to microsatellite stable (MSS) CRC. The BRAF V600E mutation worse MSS This occurs 40% of MSI CRC and it is unclear whether confers this setting. prognostic value KRAS mutations both remains unclear. We examined the effect on II III colon patients. exon 15 2–3 status was assessed 143 ( n = 85) 58) cancers by high resolution melting analysis sequencing. relation between...
Candidate immune biomarkers have been proposed for predicting response to immunotherapy in urothelial cancer (UC). Yet, these are imperfect and lack predictive power. A comprehensive overview of the tumor contexture, including Tertiary Lymphoid structures (TLS), is needed better understand UC. We analyzed sections by quantitative multiplex immunofluorescence characterize cell subsets various compartments tumors without pretreatment exposed preoperative anti-PD1/CTLA-4 checkpoint inhibitors...
The diversity of the T cell receptor (TCR) repertoire is limited, because processes positive and negative selection. To obtain cells with specificities beyond immune system's capacity, we have developed a strategy for retroviral TCR display. In this approach, library variants generated in vitro introduced into TCR-negative murine line by transfer. We document value display creation an influenza A-specific subsequent selection TCRs that either recognize parental epitope or acquired...
Abstract Purpose: There have been reports of successful treatment metastatic melanoma patients with active specific immunotherapy (ASI) using irradiated autologous tumor cell vaccination. It is still unknown why some respond and others do not. Tumor cells can evade the immune system, for example through interference antigen presentation by down-regulation MHC molecules or expressing proteins interfering cytotoxic lymphocyte–induced apoptosis like granzyme B antagonist protease inhibitor 9...