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Human CD34+-derived complete plasmacytoid and conventional dendritic cell vaccine effectively induces antigen-specific CD8+ T cell and NK cell responses in vitro and in vivo.
- Source :
- Cellular & Molecular Life Sciences; Oct2023, Vol. 80 Issue 10, p1-19, 19p
- Publication Year :
- 2023
-
Abstract
- Allogeneic stem cell transplantation (alloSCT) can be curative for hemato-oncology patients due to effective graft-versus-tumor immunity. However, relapse remains the major cause of treatment failure, emphasizing the need for adjuvant immunotherapies. In this regard, post-transplantation dendritic cell (DC) vaccination is a highly interesting strategy to boost graft-versus-tumor responses. Previously, we developed a clinically applicable protocol for simultaneous large-scale generation of end-stage blood DC subsets from donor-derived CD34<superscript>+</superscript> stem cells, including conventional type 1 and 2 DCs (cDC1s and cDC2s), and plasmacytoid DCs (pDCs). In addition, the total cultured end-product (DC-complete vaccine), also contains non-end-stage-DCs (i.e. non-DCs). In this study, we aimed to dissect the phenotypic identity of these non-DCs and their potential immune modulatory functions on the potency of cDCs and pDCs in stimulating tumor-reactive CD8<superscript>+</superscript> T and NK cell responses, in order to obtain rationale for clinical translation of our DC-complete vaccine. The non-DC compartment was heterogeneous and comprised of myeloid progenitors and (immature) granulocyte- and monocyte-like cells. Importantly, non-DCs potentiated toll-like receptor-induced DC maturation, as reflected by increased expression of co-stimulatory molecules and enhanced cDC-derived IL-12 and pDC-derived IFN-α production. Additionally, antigen-specific CD8<superscript>+</superscript> T cells effectively expanded upon DC-complete vaccination in vitro and in vivo. This effect was strongly augmented by non-DCs in an antigen-independent manner. Moreover, non-DCs did not impair in vitro DC-mediated NK cell activation, degranulation nor cytotoxicity. Notably, in vivo i.p. DC-complete vaccination activated i.v. injected NK cells. Together, these data demonstrate that the non-DC compartment potentiates DC-mediated activation and expansion of antigen-specific CD8<superscript>+</superscript> T cells and do not impair NK cell responses in vitro and in vivo. This underscores the rationale for further clinical translation of our CD34<superscript>+</superscript>-derived DC-complete vaccine in hemato-oncology patients post alloSCT. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 1420682X
- Volume :
- 80
- Issue :
- 10
- Database :
- Complementary Index
- Journal :
- Cellular & Molecular Life Sciences
- Publication Type :
- Academic Journal
- Accession number :
- 172236284
- Full Text :
- https://doi.org/10.1007/s00018-023-04923-4