title: CD8+ T cell priming by dendritic cell vaccines requires antigen transfer to endogenous antigen presenting cells.
abstract: BACKGROUND
  Immunotherapeutic strategies to stimulate anti-tumor immunity are promising approaches for cancer treatment. A major barrier to their success is the immunosuppressive microenvironment of tumors, which inhibits the functions of endogenous dendritic cells (DCs) that are necessary for the generation of anti-tumor CD8+ T cells. To overcome this problem, autologous DCs are generated ex vivo, loaded with tumor antigens, and activated in this non-suppressive environment before administration to patients. However, DC-based vaccines rarely induce tumor regression.
  
  
  RESULTS
  We examined the fate and function of these DCs following their injection using murine models, in order to better understand their interaction with the host immune system. Contrary to previous assumptions, we show that DC vaccines have an insignificant role in directly priming CD8+ T cells, but instead function primarily as vehicles for transferring antigens to endogenous antigen presenting cells, which are responsible for the subsequent activation of T cells.
  
  
  CONCLUSIONS
  This reliance on endogenous immune cells may explain the limited success of current DC vaccines to treat cancer and offers new insight into how these therapies can be improved. Future approaches should focus on creating DC vaccines that are more effective at directly priming T cells, or abrogating the tumor induced suppression of endogenous DCs.
authors.affiliation: Cancer Institute, New York University School of Medicine, New York, New York, United States of America.
authors.forename: Alice W
authors.initials: AW
authors.lastname: Yewdall
authors.forename: Scott B
authors.initials: SB
authors.lastname: Drutman
authors.forename: Felecia
authors.initials: F
authors.lastname: Jinwala
authors.forename: Keith S
authors.initials: KS
authors.lastname: Bahjat
authors.forename: Nina
authors.initials: N
authors.lastname: Bhardwaj
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D014612:Vaccines / Q000276:immunology*
chemical_list: D014612:Vaccines