Influence of heat stress on human monocyte-derived dendritic cell functions with immunotherapeutic potential for antitumor vaccines.
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.
Hatzfeld-Charbonnier
Anne Sophie
AS
INSERM U837 Université de Lille 2, 1 Place Verdun, F-59045, Lille Cedex, France, and Department of Medical Oncology, Erasme Hospital, Brussels, Belgium.
Lasek
Audrey
A
Castera
Laurent
L
Gosset
Philippe
P
Velu
Thierry
T
Formstecher
Pierre
P
Mortier
Laurent
L
Marchetti
Philippe
P
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
C515460:CCL19 protein, human; D019496:Cancer Vaccines; D054415:Chemokine CCL19; D019742:Chemokines, CC; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12