4 results on '"Schaap, Nicolaas P. M."'
Search Results
2. Clinically applicable CD34+-derived blood dendritic cell subsets exhibit key subset-specific features and potently boost anti-tumor T and NK cell responses
- Author
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van Eck van der Sluijs, Jesper, van Ens, Diede, Thordardottir, Soley, Vodegel, Denise, Hermens, Inge, van der Waart, Anniek B., Falkenburg, J. H. Frederik, Kester, Michel G. D., de Rink, Iris, Heemskerk, Mirjam H. M., Borst, Jannie, Schaap, Nicolaas P. M., Jansen, Joop H., Xiao, Yanling, Dolstra, Harry, and Hobo, Willemijn
- Subjects
CD34+ hematopoietic progenitor cells ,Cancer Research ,T-Lymphocytes ,Cancer development and immune defence Radboud Institute for Molecular Life Sciences [Radboudumc 2] ,medicine.medical_treatment ,Immunology ,Cell ,Cell Culture Techniques ,T cells ,CD34 ,Antigens, CD34 ,CD34(+) hematopoietic progenitor cells ,NK cells ,Biology ,Lymphocyte Activation ,Dendritic cells ,03 medical and health sciences ,Cross-Priming ,0302 clinical medicine ,Immunity ,medicine ,Humans ,Immunology and Allergy ,030304 developmental biology ,Antigen Presentation ,0303 health sciences ,Vaccination ,Dendritic cell ,Immunotherapy ,Hematopoietic Stem Cells ,Acquired immune system ,Clinical application ,Killer Cells, Natural ,Transplantation ,medicine.anatomical_structure ,Oncology ,Cancer research ,Original Article ,Stem cell ,030215 immunology - Abstract
Allogeneic stem cell transplantation (alloSCT), following induction chemotherapy, can be curative for hemato-oncology patients due to powerful graft-versus-tumor immunity. However, disease recurrence remains the major cause of treatment failure, emphasizing the need for potent adjuvant immunotherapy. In this regard, dendritic cell (DC) vaccination is highly attractive, as DCs are the key orchestrators of innate and adaptive immunity. Natural DC subsets are postulated to be more powerful compared with monocyte-derived DCs, due to their unique functional properties and cross-talk capacity. Yet, obtaining sufficient numbers of natural DCs, particularly type 1 conventional DCs (cDC1s), is challenging due to low frequencies in human blood. We developed a clinically applicable culture protocol using donor-derived G-CSF mobilized CD34+ hematopoietic progenitor cells (HPCs) for simultaneous generation of high numbers of cDC1s, cDC2s and plasmacytoid DCs (pDCs). Transcriptomic analyses demonstrated that these ex vivo-generated DCs highly resemble their in vivo blood counterparts. In more detail, we demonstrated that the CD141+CLEG9A+ cDC1 subset exhibited key features of in vivo cDC1s, reflected by high expression of co-stimulatory molecules and release of IL-12p70 and TNF-α. Furthermore, cDC1s efficiently primed alloreactive T cells, potently cross-presented long-peptides and boosted expansion of minor histocompatibility antigen-experienced T cells. Moreover, they strongly enhanced NK cell activation, degranulation and anti-leukemic reactivity. Together, we developed a robust culture protocol to generate highly functional blood DC subsets for in vivo application as tailored adjuvant immunotherapy to boost innate and adaptive anti-tumor immunity in alloSCT patients.
- Published
- 2021
3. Clinically applicable CD34+-derived blood dendritic cell subsets exhibit key subset-specific features and potently boost anti-tumor T and NK cell responses.
- Author
-
van Eck van der Sluijs, Jesper, van Ens, Diede, Thordardottir, Soley, Vodegel, Denise, Hermens, Inge, van der Waart, Anniek B., Falkenburg, J. H. Frederik, Kester, Michel G. D., de Rink, Iris, Heemskerk, Mirjam H. M., Borst, Jannie, Schaap, Nicolaas P. M., Jansen, Joop H., Xiao, Yanling, Dolstra, Harry, and Hobo, Willemijn
- Subjects
KILLER cells ,BLOOD cells ,DENDRITIC cells ,T cells ,PROGENITOR cells - Abstract
Allogeneic stem cell transplantation (alloSCT), following induction chemotherapy, can be curative for hemato-oncology patients due to powerful graft-versus-tumor immunity. However, disease recurrence remains the major cause of treatment failure, emphasizing the need for potent adjuvant immunotherapy. In this regard, dendritic cell (DC) vaccination is highly attractive, as DCs are the key orchestrators of innate and adaptive immunity. Natural DC subsets are postulated to be more powerful compared with monocyte-derived DCs, due to their unique functional properties and cross-talk capacity. Yet, obtaining sufficient numbers of natural DCs, particularly type 1 conventional DCs (cDC1s), is challenging due to low frequencies in human blood. We developed a clinically applicable culture protocol using donor-derived G-CSF mobilized CD34
+ hematopoietic progenitor cells (HPCs) for simultaneous generation of high numbers of cDC1s, cDC2s and plasmacytoid DCs (pDCs). Transcriptomic analyses demonstrated that these ex vivo-generated DCs highly resemble their in vivo blood counterparts. In more detail, we demonstrated that the CD141+ CLEG9A+ cDC1 subset exhibited key features of in vivo cDC1s, reflected by high expression of co-stimulatory molecules and release of IL-12p70 and TNF-α. Furthermore, cDC1s efficiently primed alloreactive T cells, potently cross-presented long-peptides and boosted expansion of minor histocompatibility antigen-experienced T cells. Moreover, they strongly enhanced NK cell activation, degranulation and anti-leukemic reactivity. Together, we developed a robust culture protocol to generate highly functional blood DC subsets for in vivo application as tailored adjuvant immunotherapy to boost innate and adaptive anti-tumor immunity in alloSCT patients. [ABSTRACT FROM AUTHOR]- Published
- 2021
- Full Text
- View/download PDF
4. Cell composition and expansion strategy can reduce the beneficial effect of AKT-inhibition on functionality of CD8+ T cells.
- Author
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Mousset, Charlotte M., Hobo, Willemijn, de Ligt, Aafke, Baardman, Sjoerd, Schaap, Nicolaas P. M., Jansen, Joop H., van der Waart, Anniek B., and Dolstra, Harry
- Subjects
T cells ,STEM cells ,CELLULAR therapy ,LYMPHOCYTES - Abstract
AKT-inhibition is a promising approach to improve T cell therapies; however, its effect on CD4
+ T cells is insufficiently explored. Previously, we and others showed that AKT-inhibition during ex vivo CD8+ T cell expansion facilitates the generation of polyfunctional T cells with stem cell memory-like traits. However, most therapeutic T cell products are generated from lymphocytes, containing CD4+ T cells that can affect CD8+ T cells dependent on the Th-subset. Here, we investigated the effect of AKT-inhibition on CD4+ T cells, during separate as well as total T cell expansions. Interestingly, ex vivo AKT-inhibition preserved the early memory phenotype of CD4+ T cells based on higher CD62L, CXCR4 and CCR7 expression. However, in the presence of AKT-inhibition, Th-differentiation was skewed toward more Th2-associated at the expense of Th1-associated cells. Importantly, the favorable effect of AKT-inhibition on the functionality of CD8+ T cells drastically diminished in the presence of CD4+ T cells. Moreover, also the expansion method influenced the effect of AKT-inhibition on CD8+ T cells. These findings indicate that the effect of AKT-inhibition on CD8+ T cells is dependent on cell composition and expansion strategy, where presence of CD4+ T cells as well as polyclonal stimulation impede the favorable effect of AKT-inhibition. [ABSTRACT FROM AUTHOR]- Published
- 2020
- Full Text
- View/download PDF
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