Primary Human Blood Dendritic Cells for Cancer Immunotherapy-Tailoring the Immune Response by Dendritic Cell Maturation

Overview

Journal Biomedicines

Specialty Biomedical Engineering

Date 2017 May 25

PMID 28536413

Citations 14

Authors

Simone P Sittig

I Jolanda M de Vries

Gerty Schreibelt

Affiliations

Soon will be listed here.

Abstract

Dendritic cell (DC)-based cancer vaccines hold the great promise of tipping the balance from tolerance of the tumor to rejection. In the last two decades, we have gained tremendous knowledge about DC-based cancer vaccines. The maturation of DCs has proven indispensable to induce immunogenic T cell responses. We review the insights gained from the development of maturation cocktails in monocyte derived DC-based trials. More recently, we have also gained insights into the functional specialization of primary human blood DC subsets. In peripheral human blood, we can distinguish at least three primary DC subsets, namely CD1c⁺ and CD141⁺ myeloid DCs and plasmacytoid DCs. We reflect the current knowledge on maturation and T helper polarization by these blood DC subsets in the context of DC-based cancer vaccines. The maturation stimulus in combination with the DC subset will determine the type of T cell response that is induced. First trials with these natural DCs underline their excellent functioning and mark them as promising tools for future vaccination strategies.

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References

Swiecki M, Colonna M . Unraveling the functions of plasmacytoid dendritic cells during viral infections, autoimmunity, and tolerance. Immunol Rev. 2010; 234(1):142-62. PMC: 3507434. DOI: 10.1111/j.0105-2896.2009.00881.x. View

Spranger S, Javorovic M, Burdek M, Wilde S, Mosetter B, Tippmer S . Generation of Th1-polarizing dendritic cells using the TLR7/8 agonist CL075. J Immunol. 2010; 185(1):738-47. DOI: 10.4049/jimmunol.1000060. View

Tel J, Lambeck A, Cruz L, Tacken P, de Vries I, Figdor C . Human plasmacytoid dendritic cells phagocytose, process, and present exogenous particulate antigen. J Immunol. 2010; 184(8):4276-83. DOI: 10.4049/jimmunol.0903286. View

Prue R, Vari F, Radford K, Tong H, Hardy M, DRozario R . A phase I clinical trial of CD1c (BDCA-1)+ dendritic cells pulsed with HLA-A*0201 peptides for immunotherapy of metastatic hormone refractory prostate cancer. J Immunother. 2015; 38(2):71-6. DOI: 10.1097/CJI.0000000000000063. View

Di Pucchio T, Chatterjee B, Smed-Sorensen A, Clayton S, Palazzo A, Montes M . Direct proteasome-independent cross-presentation of viral antigen by plasmacytoid dendritic cells on major histocompatibility complex class I. Nat Immunol. 2008; 9(5):551-7. PMC: 2695657. DOI: 10.1038/ni.1602. View

Vanneman M, Dranoff G . Combining immunotherapy and targeted therapies in cancer treatment. Nat Rev Cancer. 2012; 12(4):237-51. PMC: 3967236. DOI: 10.1038/nrc3237. View

Schreibelt G, Klinkenberg L, Cruz L, Tacken P, Tel J, Kreutz M . The C-type lectin receptor CLEC9A mediates antigen uptake and (cross-)presentation by human blood BDCA3+ myeloid dendritic cells. Blood. 2012; 119(10):2284-92. DOI: 10.1182/blood-2011-08-373944. View

Uematsu S, Akira S . Toll-Like receptors (TLRs) and their ligands. Handb Exp Pharmacol. 2007; (183):1-20. DOI: 10.1007/978-3-540-72167-3_1. View

Jahrsdorfer B, Weiner G . CpG oligodeoxynucleotides as immunotherapy in cancer. Update Cancer Ther. 2009; 3(1):27-32. PMC: 2390897. DOI: 10.1016/j.uct.2007.11.003. View

10.

Montoya M, Schiavoni G, Mattei F, Gresser I, Belardelli F, Borrow P . Type I interferons produced by dendritic cells promote their phenotypic and functional activation. Blood. 2002; 99(9):3263-71. DOI: 10.1182/blood.v99.9.3263. View

11.

Pan J, Zhang M, Wang J, Wang Q, Xia D, Sun W . Interferon-gamma is an autocrine mediator for dendritic cell maturation. Immunol Lett. 2004; 94(1-2):141-51. DOI: 10.1016/j.imlet.2004.05.003. View

12.

Salio M, Cella M, Vermi W, Facchetti F, Palmowski M, Smith C . Plasmacytoid dendritic cells prime IFN-gamma-secreting melanoma-specific CD8 lymphocytes and are found in primary melanoma lesions. Eur J Immunol. 2003; 33(4):1052-62. DOI: 10.1002/eji.200323676. View

13.

Mathan T, Figdor C, Buschow S . Human plasmacytoid dendritic cells: from molecules to intercellular communication network. Front Immunol. 2013; 4:372. PMC: 3825182. DOI: 10.3389/fimmu.2013.00372. View

14.

Hoeffel G, Ripoche A, Matheoud D, Nascimbeni M, Escriou N, Lebon P . Antigen crosspresentation by human plasmacytoid dendritic cells. Immunity. 2007; 27(3):481-92. DOI: 10.1016/j.immuni.2007.07.021. View

15.

Le Bon A, Etchart N, Rossmann C, Ashton M, Hou S, Gewert D . Cross-priming of CD8+ T cells stimulated by virus-induced type I interferon. Nat Immunol. 2003; 4(10):1009-15. DOI: 10.1038/ni978. View

16.

Nierkens S, den Brok M, Roelofsen T, Wagenaars J, Figdor C, Ruers T . Route of administration of the TLR9 agonist CpG critically determines the efficacy of cancer immunotherapy in mice. PLoS One. 2009; 4(12):e8368. PMC: 2791230. DOI: 10.1371/journal.pone.0008368. View

17.

Meixlsperger S, Leung C, Ramer P, Pack M, Vanoaica L, Breton G . CD141+ dendritic cells produce prominent amounts of IFN-α after dsRNA recognition and can be targeted via DEC-205 in humanized mice. Blood. 2013; 121(25):5034-44. PMC: 3689250. DOI: 10.1182/blood-2012-12-473413. View

18.

Hofmann M, Kors C, Audring H, Walden P, Sterry W, Trefzer U . Phase 1 evaluation of intralesionally injected TLR9-agonist PF-3512676 in patients with basal cell carcinoma or metastatic melanoma. J Immunother. 2008; 31(5):520-7. DOI: 10.1097/CJI.0b013e318174a4df. View

19.

Boullart A, Aarntzen E, Verdijk P, Jacobs J, Schuurhuis D, Benitez-Ribas D . Maturation of monocyte-derived dendritic cells with Toll-like receptor 3 and 7/8 ligands combined with prostaglandin E2 results in high interleukin-12 production and cell migration. Cancer Immunol Immunother. 2008; 57(11):1589-97. PMC: 2522299. DOI: 10.1007/s00262-008-0489-2. View

20.

Nizzoli G, Krietsch J, Weick A, Steinfelder S, Facciotti F, Gruarin P . Human CD1c+ dendritic cells secrete high levels of IL-12 and potently prime cytotoxic T-cell responses. Blood. 2013; 122(6):932-42. DOI: 10.1182/blood-2013-04-495424. View