title: Potential approaches for more successful dendritic cell-based immunotherapy.
abstract: BACKGROUND
  Dendritic cells (DCs) are the most important antigen-presenting cell population for activating antitumor T-cell responses; therefore, they offer a unique opportunity for specific targeting of tumors.
  
  
  METHODS
  We will discuss the critical factors for the enhancement of DC vaccine efficacy: different DC subsets, types of in vitro DC manufacturing protocol, types of tumor antigen to be loaded and finally different adjuvants for activating them. We will cover potential combinatorial strategies with immunomodulatory therapies: depleting T-regulatory (Treg) cells, blocking VEGF and blocking inhibitory signals. Furthermore, recommendations to incorporate these criteria into DC-based tumor immunotherapy will be suggested.
  
  
  CONCLUSIONS
  Monocyte-derived DCs are the most widely used DC subset in the clinic, whereas Langerhans cells and plasmacytoid DCs are two emerging DC subsets that are highly effective in eliciting cytotoxic T lymphocyte responses. Depending on the type of tumor antigens selected for loading DCs, it is important to optimize a protocol that will generate highly potent DCs. The future aim of DC-based immunotherapy is to combine it with one or more immunomodulatory therapies, for example, Treg cell depletion, VEGF blockage and T-cell checkpoint blockage, to elicit the most optimal antitumor immunity to induce long-term remission or even cure cancer patients.
authors.affiliation: University of Pennsylvania Medical Center, Ovarian Cancer Research Center , Philadelphia, PA 19104 , USA Lana.Kandalaft@chuv.ch ; cheryl_chiang@yahoo.com.
authors.forename: Cheryl Lai-Lai
authors.initials: CL
authors.lastname: Chiang
authors.forename: Klara
authors.initials: K
authors.lastname: Balint
authors.forename: George
authors.initials: G
authors.lastname: Coukos
authors.forename: Lana E
authors.initials: LE
authors.lastname: Kandalaft
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000637:transplantation; D019496:Cancer Vaccines / Q000276:immunology / Q000627:therapeutic use; D064987:Cell- and Tissue-Based Therapy / Q000379:methods* / Q000639:trends; D003713:Dendritic Cells / Q000276:immunology / Q000637:transplantation*; D006801:Humans; D007167:Immunotherapy / Q000379:methods* / Q000639:trends; D009000:Monocytes / Q000276:immunology / Q000637:transplantation; D009369:Neoplasms / Q000276:immunology / Q000628:therapy; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000637:transplantation; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000637:transplantation
chemical_list: D019496:Cancer Vaccines
keywords: cancer; dendritic cell; immunotherapy; vaccines