Plasmacytoid Dendritic Cells as a Novel Cell-Based Cancer Immunotherapy
Abstract
:1. Introduction
2. pDC Biology: Phenotype and Function
3. pDCs in Cancer
3.1. Impairment of pDCs in the TME
3.2. pDCs in Antitumor Immunity
4. pDC-Based Cancer Immunotherapy
4.1. Immunotherapy Strategies Based on Activation of TLR Signalling
4.2. DC Mobilization for Cancer Immunotherapy
4.3. pDC-Based Vaccines for Cancer Immunotherapy
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Abbreviations
APC | Antigen-presenting cell |
BM | Bone marrow |
BMT | Bone marrow transplantation |
BST2 | Bone marrow stromal antigen 2 |
CBT | Cord blood transplantation |
cDCs | Conventional DCs |
CLR | C-type lectin-like receptors |
CRPC | Castration-resistant prostate cancer |
CTLs | CD8+ cytotoxic T lymphocytes |
CXCL | C-X-C motif chemokine ligands |
CXCR3 | C-X-C motif chemokine receptor 3 |
DCs | Dendritic cells |
Flt3L | Fms-like tyrosine kinase 3-ligand |
GM-CSF | Granulocyte-macrophage colony stimulating factor |
HNSCC | Head and neck squamous cell carcinomas |
HSPCs | Hematopoietic stem and progenitor cells |
IDO | Immunoregulatory enzyme indoleamine 2,3-dioxygenase |
IFN-I | Type I Interferon |
IFNR | IFN receptor |
IL-3 | Interleukin 3 |
ILT7 | Immunoglobulin-like cell transcript 7 |
IMQ | Imiquimod |
IRF | Interferon Regulatory Factor |
MHC | Major histocompatibility complex |
moDCs | Monocyte-derived dendritic cells |
NK | Natural killer |
OS | Overall survival |
PBMCs | Peripheral blood mononuclear cells |
pDCs | Plasmacytoid DCs |
PFS | Progression-free survival |
PGE2 | Prostaglandin E2 |
SLN | Sentinel lymph node |
TAA | Tumor-associated antigens |
TGF-β | Transforming growth factor- β |
TILs | Tumor-infiltrating lymphocytes |
TLR | Toll-like receptors |
TME | Tumor microenvironment |
TNF | Tumor necrosis factor |
TRAIL-R2 | TRAIL receptor-2 |
Treg | Regulatory T cells |
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Clinical Trial Identifier | Recruitment Status | Principal Investigator | Institution | Condition | Phase | Number of Participants | Therapeutic Product | Dose | Toxicity | Immune Response Observed | Clinical Outcome | References |
---|---|---|---|---|---|---|---|---|---|---|---|---|
NCT01690377 | Completed | C J A Punt | Radboud University Medical Center | Metastatic melanoma | phase I | 15 | Natural circulating pDCs loaded with peptides derived from melanoma TAAs | 0.3–3 × 106 pDCs/injection | Grade 1 flu-like symptoms | Upregulation of CD80, CD83, CD86, MHC class I, and class II in activated pDCs Migration of activated pDCs in vivo Tumor-specific CD4+ and CD8+ T-cell responses | Median PFS: 4 months Median OS: 22 months | Tel, Aarntzen et al., 2013 [29] |
C G Figdor | ||||||||||||
NCT01863108 | Completed | J Plumas | Grenoble University Hospital | Metastatic stage IV melanoma | phase I | 9 | GeniusVac-Mel4: allogeneic PDC line loaded with four melanoma TAAs | 4–60 × 106 pDCs/injection | General disorders. Administration site events. Other adverse events (i.e., nausea, abdominal pain, and decreased appetite). Grade 3 adverse events (pain and lymphadenitis). | Antigen-specific T cells Recruitment of anti-vaccine T cells into the tumor bed | Stable disease for 16 to 48 weeks in 4 patients | Charles, Chaperot et al., 2020 [31] |
J Charles | ||||||||||||
NCT02692976 | Completed | W R Gerritsen | Radboud University Nijmegen Medical Centre | Prostatic Neoplasms | phase IIa | 21 | cDC2, pDCs or a combination of both loaded with three prostate TAAs |
| Grade 1–2 toxicity (flu-like symptoms, fatigue, upper respiratory infections, injection site reactions, etc.) | Antigen-specific T cells with no significant differences between treatments IFN-γ production | Median PFS for all patients: 9.5 months Median OS: not reached | Westdorp, Creemers et al., 2019 [30] |
F Witjes | ||||||||||||
J de Vries | ||||||||||||
NCT04212377 | Completed | J de Vries | Radboud University Medical Center | Metastatic Endometrial Cancer | phase II | 8 | cDC2 and pDCs loaded with TAAs | |||||
NCT03970746 | Recruiting | J Vansteenkiste | PDC*line Pharma | Non-small-cell lung cancer | phase I/II | Allogeneic PDC line loaded with TAAs |
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Hernández, S.S.; Jakobsen, M.R.; Bak, R.O. Plasmacytoid Dendritic Cells as a Novel Cell-Based Cancer Immunotherapy. Int. J. Mol. Sci. 2022, 23, 11397. https://doi.org/10.3390/ijms231911397
Hernández SS, Jakobsen MR, Bak RO. Plasmacytoid Dendritic Cells as a Novel Cell-Based Cancer Immunotherapy. International Journal of Molecular Sciences. 2022; 23(19):11397. https://doi.org/10.3390/ijms231911397
Chicago/Turabian StyleHernández, Sabina Sánchez, Martin Roelsgaard Jakobsen, and Rasmus O. Bak. 2022. "Plasmacytoid Dendritic Cells as a Novel Cell-Based Cancer Immunotherapy" International Journal of Molecular Sciences 23, no. 19: 11397. https://doi.org/10.3390/ijms231911397