immunotherapy
Conditions
Interventions
None listed
Sponsors
Academisch Medisch Centrum
Eligibility
Age
2 Years to 17 Years
Inclusion criteria
Inclusion criteria: High risk neuroblastoma, between 1 and 18 years at diagnosis Neuroblastoma histological proven diagnosis Informed consent Initial staging of the tumor No pregnancy
Exclusion criteria
Exclusion criteria: Any prior anticancer treatment
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| if the BM sample is infiltrated by NBL cells, the expression of activating NK cell receptor ligands on the tumor itself; such as MIC (MICA/B) and ULBP (ULBP1-4) proteins and CD112-/ CD155 as well as the expression of HLA class I (inhibitory liogand), CD54-/CD58 (adhesion) will be evaluated bij FACS analysis using multiple markers. NK cell sensitivity will be determined by labelling primary NBL cells with 51-Chromium or by chemo luminescent methods and adding resting and cytokine actyivated NK cells. Furthermore, if NK cell cytotoxicity occurs, activating NK cell receptors will be blocked by monocklonal antibodies (NKG2D, DNAM-1), thereby allowing amnalysis of the activating signals involved. peripheral blood samples of newly diagnosed, treated and during FU of HR NBL patients will allow analysis of NK cell phenotype and function in these patients. Phenotyping The presence of a variety of lymphocyte subsets (e.g. standard T-cell subset, dendritic cells, lineages of suppressor cells) has been described to be associated with either response or failure of therapy in cancer patients, including those treated with IL-2 or GM-CSF. For the present proposal we will study the number and differentiation of each subset present in the HR NBL patients in different stages of the disease/treatment regimen. Immunophenotyping will be performed on biobanked peripheral blood and available bone marrow aspirates using flow cytometry to visualize subsets of: 1. T cells (naïve, central/effector memory, resting or activated CD4, CD8 and gamma/delta TCR) 2. Regulatory T cells (CD3/CD4/CD127/CD25/FoxP3) 3. T helper subsets (Th1, Th2, Th17, Th22) 4. B cells (naïve, memory, transitional, plasmablasts) 5. NK/NKT cells (CD16/CD56, CD3, Va24/Vb11) 6. DC/mono ((non-)classismal monocytesm, cDC and pDC) 7. Myeloid-derived (suppressor) cells and Tr1 cells Secretome Analyzing the profile of secreted cytokines, chemokines and growth factors represents an integral part of im | — |
Countries
Netherlands
Outcome results
None listed