Program DHC-Virtual
20 - 21 January 2021
Abstracts Immunology session 4
Abstract
CD34+-derived DC subsets exhibit subset-specific features and boost anti-tumor immunity
21 January
10:00 10:12
J. van Eck van der Sluijs
Paper

Clinically applicable CD34+-derived blood dendritic cell subsets exhibit key subset-specific features and potently boost tumor-reactive T and NK cell responses 

Jesper van Eck van der Sluijs (1), Diede van Ens (1), Soley Thordardottir (1), Denise Vodegel (1), Inge Hermens (1), Anniek van der Waart (1), Frederik Falkenburg (2), Michel Kester (2), Iris de Rink (3), Mirjam Heemskerk (2), Jannie Borst (4), Michel Schaap (1), Joop Jansen (1), Yanling Xiao (4), Harry Dolstra (1), Willemijn Hobo (1)
(1) Radboudumc, Laboratory Medicine, Nijmegen, (2) LUMC, Hematoloy, Leiden, (3) NKI, Genomics Core Facility, Amsterdam, (4) LUMC, Immunohematology and blood transfusion, Leiden
No potential conflicts of interest
Introduction

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.

Methods

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). 

Results

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.

Conclusion

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.

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