title: Dendritic Cells as Pharmacological Tools for Cancer Immunotherapy.
abstract: Although the earliest—rudimentary—attempts at exploiting the immune system for cancer therapy can be traced back to the late 18th Century, it was not until the past decade that cancer immunotherapeutics have truly entered mainstream clinical practice. Given their potential to stimulate both adaptive and innate antitumor immune responses, dendritic cells (DCs) have come under intense scrutiny in recent years as pharmacological tools for cancer immunotherapy. Conceptually, the clinical effectiveness of this form of active immunotherapy relies on the completion of three critical steps: 1) the DCs used as immunotherapeutic vehicles must properly activate the antitumor immune effector cells of the host, 2) these immune effector cells must be receptive to stimulation by the DCs and be competent to mediate their antitumor effects, which 3) requires overcoming the various immune-inhibitory mechanisms used by the tumor cells. In this review, following a brief overview of the pivotal milestones in the history of cancer immunotherapy, we will introduce the reader to the basic immunobiological and pharmacological principles of active cancer immunotherapy using DCs. We will then discuss how current research is trying to define the optimal parameters for each of the above steps to realize the full clinical potential of DC therapeutics. Given its high suitability for immune interventions, acute myeloid leukemia was chosen here to showcase the latest research trends driving the field of DC-based cancer immunotherapy.
authors.affiliation: Faculty of Medicine and Health Sciences, Vaccine & Infectious Disease Institute, Laboratory of Experimental Hematology, Tumor Immunology Group (S.A., H.H.V.A., H.G., E.L., V.F.V.T., Z.N.B.), and Faculty of Medicine and Health Sciences, Center for Oncological Research (E.L.S.), University of Antwerp, Antwerp, Belgium; Center for Cell Therapy & Regenerative Medicine, Antwerp University Hospital, Antwerp, Belgium (S.A., E.L.S., Z.N.B.); and ANZAC Research Institute, Dendritic Cell Biology and Therapeutics Group, University of Sydney, Sydney, New South Wales, Australia (C.B., P.D.F.) sebastien.anguille@uantwerp.be.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Anguille
authors.affiliation: Faculty of Medicine and Health Sciences, Vaccine & Infectious Disease Institute, Laboratory of Experimental Hematology, Tumor Immunology Group (S.A., H.H.V.A., H.G., E.L., V.F.V.T., Z.N.B.), and Faculty of Medicine and Health Sciences, Center for Oncological Research (E.L.S.), University of Antwerp, Antwerp, Belgium; Center for Cell Therapy & Regenerative Medicine, Antwerp University Hospital, Antwerp, Belgium (S.A., E.L.S., Z.N.B.); and ANZAC Research Institute, Dendritic Cell Biology and Therapeutics Group, University of Sydney, Sydney, New South Wales, Australia (C.B., P.D.F.).
authors.forename: Evelien L
authors.initials: EL
authors.lastname: Smits
authors.affiliation: Faculty of Medicine and Health Sciences, Vaccine & Infectious Disease Institute, Laboratory of Experimental Hematology, Tumor Immunology Group (S.A., H.H.V.A., H.G., E.L., V.F.V.T., Z.N.B.), and Faculty of Medicine and Health Sciences, Center for Oncological Research (E.L.S.), University of Antwerp, Antwerp, Belgium; Center for Cell Therapy & Regenerative Medicine, Antwerp University Hospital, Antwerp, Belgium (S.A., E.L.S., Z.N.B.); and ANZAC Research Institute, Dendritic Cell Biology and Therapeutics Group, University of Sydney, Sydney, New South Wales, Australia (C.B., P.D.F.).
authors.forename: Christian
authors.initials: C
authors.lastname: Bryant
authors.affiliation: Faculty of Medicine and Health Sciences, Vaccine & Infectious Disease Institute, Laboratory of Experimental Hematology, Tumor Immunology Group (S.A., H.H.V.A., H.G., E.L., V.F.V.T., Z.N.B.), and Faculty of Medicine and Health Sciences, Center for Oncological Research (E.L.S.), University of Antwerp, Antwerp, Belgium; Center for Cell Therapy & Regenerative Medicine, Antwerp University Hospital, Antwerp, Belgium (S.A., E.L.S., Z.N.B.); and ANZAC Research Institute, Dendritic Cell Biology and Therapeutics Group, University of Sydney, Sydney, New South Wales, Australia (C.B., P.D.F.).
authors.forename: Heleen H
authors.initials: HH
authors.lastname: Van Acker
authors.affiliation: Faculty of Medicine and Health Sciences, Vaccine & Infectious Disease Institute, Laboratory of Experimental Hematology, Tumor Immunology Group (S.A., H.H.V.A., H.G., E.L., V.F.V.T., Z.N.B.), and Faculty of Medicine and Health Sciences, Center for Oncological Research (E.L.S.), University of Antwerp, Antwerp, Belgium; Center for Cell Therapy & Regenerative Medicine, Antwerp University Hospital, Antwerp, Belgium (S.A., E.L.S., Z.N.B.); and ANZAC Research Institute, Dendritic Cell Biology and Therapeutics Group, University of Sydney, Sydney, New South Wales, Australia (C.B., P.D.F.).
authors.forename: Herman
authors.initials: H
authors.lastname: Goossens
authors.affiliation: Faculty of Medicine and Health Sciences, Vaccine & Infectious Disease Institute, Laboratory of Experimental Hematology, Tumor Immunology Group (S.A., H.H.V.A., H.G., E.L., V.F.V.T., Z.N.B.), and Faculty of Medicine and Health Sciences, Center for Oncological Research (E.L.S.), University of Antwerp, Antwerp, Belgium; Center for Cell Therapy & Regenerative Medicine, Antwerp University Hospital, Antwerp, Belgium (S.A., E.L.S., Z.N.B.); and ANZAC Research Institute, Dendritic Cell Biology and Therapeutics Group, University of Sydney, Sydney, New South Wales, Australia (C.B., P.D.F.).
authors.forename: Eva
authors.initials: E
authors.lastname: Lion
authors.affiliation: Faculty of Medicine and Health Sciences, Vaccine & Infectious Disease Institute, Laboratory of Experimental Hematology, Tumor Immunology Group (S.A., H.H.V.A., H.G., E.L., V.F.V.T., Z.N.B.), and Faculty of Medicine and Health Sciences, Center for Oncological Research (E.L.S.), University of Antwerp, Antwerp, Belgium; Center for Cell Therapy & Regenerative Medicine, Antwerp University Hospital, Antwerp, Belgium (S.A., E.L.S., Z.N.B.); and ANZAC Research Institute, Dendritic Cell Biology and Therapeutics Group, University of Sydney, Sydney, New South Wales, Australia (C.B., P.D.F.).
authors.forename: Phillip D
authors.initials: PD
authors.lastname: Fromm
authors.forename: Derek N
authors.initials: DN
authors.lastname: Hart
authors.affiliation: Faculty of Medicine and Health Sciences, Vaccine & Infectious Disease Institute, Laboratory of Experimental Hematology, Tumor Immunology Group (S.A., H.H.V.A., H.G., E.L., V.F.V.T., Z.N.B.), and Faculty of Medicine and Health Sciences, Center for Oncological Research (E.L.S.), University of Antwerp, Antwerp, Belgium; Center for Cell Therapy & Regenerative Medicine, Antwerp University Hospital, Antwerp, Belgium (S.A., E.L.S., Z.N.B.); and ANZAC Research Institute, Dendritic Cell Biology and Therapeutics Group, University of Sydney, Sydney, New South Wales, Australia (C.B., P.D.F.).
authors.forename: Viggo F
authors.initials: VF
authors.lastname: Van Tendeloo
authors.affiliation: Faculty of Medicine and Health Sciences, Vaccine & Infectious Disease Institute, Laboratory of Experimental Hematology, Tumor Immunology Group (S.A., H.H.V.A., H.G., E.L., V.F.V.T., Z.N.B.), and Faculty of Medicine and Health Sciences, Center for Oncological Research (E.L.S.), University of Antwerp, Antwerp, Belgium; Center for Cell Therapy & Regenerative Medicine, Antwerp University Hospital, Antwerp, Belgium (S.A., E.L.S., Z.N.B.); and ANZAC Research Institute, Dendritic Cell Biology and Therapeutics Group, University of Sydney, Sydney, New South Wales, Australia (C.B., P.D.F.).
authors.forename: Zwi N
authors.initials: ZN
authors.lastname: Berneman
mesh_terms: D019264:Adoptive Transfer / Q000379:methods; D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm / Q000276:immunology; D017209:Apoptosis; D019496:Cancer Vaccines / Q000276:immunology; D018929:Cell Culture Techniques; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004333:Drug Administration Routes; D006801:Humans; D016233:Immunotherapy, Active / Q000379:methods*; D007694:Killer Cells, Natural / Q000276:immunology; D008285:Major Histocompatibility Complex / Q000276:immunology; D009369:Neoplasms / Q000276:immunology* / Q000628:therapy*; D015398:Signal Transduction; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D016207:Cytokines