title: Influence of heat stress on human monocyte-derived dendritic cell functions with immunotherapeutic potential for antitumor vaccines.
abstract: Mild heat stress can modulate the activities of immune cells, including dendritic cells (DC) and theoretically, would constitute an innovative approach capable of enhancing the antitumor functions of DC. Therefore, we tested the effects of mild heat stress on the physiology and viability of human monocyte-derived DC, the major type of DC used in tumor immunotherapy trials. We first designed a heat-stress protocol consisting of repetitive, sublethal heat shocks throughout the generation of DC. Using this protocol, we observed that heat stress did not perturb the morphology and the phenotype of immature or mature DC or the capacities of immature DC to uptake antigens efficiently. It is noteworthy that in response to heat stress, mature DC produced higher levels of IL-12p70 and TNF-alpha, which are two cytokines involved in the stimulation of inflammatory reaction, whereas IL-10 production remained low. After heat-stress exposure, mature DC have the full ability to stimulate naive T cells with Th1 response polarization (high IFN-gamma and low IL-4 production) in an allogeneic MLR. It is interesting that heat stress enhanced the migratory capacities of DC in response to MIP-3beta/CCL19. Finally, heat stress partly protected DC from apoptosis induced by cytokine withdrawal. Overall, these findings validate the feasibility of improving immune response by heating human monocyte-derived DC and provide a strong rationale for using mild heat stress in combination with DC vaccination to increase antitumor response.
authors.affiliation: INSERM U837 Université de Lille 2, 1 Place Verdun, F-59045, Lille Cedex, France, and Department of Medical Oncology, Erasme Hospital, Brussels, Belgium.
authors.forename: Anne Sophie
authors.initials: AS
authors.lastname: Hatzfeld-Charbonnier
authors.forename: Audrey
authors.initials: A
authors.lastname: Lasek
authors.forename: Laurent
authors.initials: L
authors.lastname: Castera
authors.forename: Philippe
authors.initials: P
authors.lastname: Gosset
authors.forename: Thierry
authors.initials: T
authors.lastname: Velu
authors.forename: Pierre
authors.initials: P
authors.lastname: Formstecher
authors.forename: Laurent
authors.initials: L
authors.lastname: Mortier
authors.forename: Philippe
authors.initials: P
authors.lastname: Marchetti
mesh_terms: D017209:Apoptosis / Q000276:immunology; D019496:Cancer Vaccines / Q000276:immunology*; D002465:Cell Movement / Q000276:immunology; D002470:Cell Survival / Q000276:immunology; D054415:Chemokine CCL19; D019742:Chemokines, CC / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology*; D018869:Heat-Shock Response / Q000276:immunology*; D006801:Humans; D007167:Immunotherapy; D018664:Interleukin-12 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D009000:Monocytes / Q000276:immunology*; D010641:Phenotype; D013329:Structure-Activity Relationship; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: C515460:CCL19 protein, human; D019496:Cancer Vaccines; D054415:Chemokine CCL19; D019742:Chemokines, CC; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12