Published online before print February 20, 2007

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(Journal of Leukocyte Biology. 2007;81:1179-1187.)
© 2007 by Society for Leukocyte Biology

Influence of heat stress on human monocyte-derived dendritic cell functions with immunotherapeutic potential for antitumor vaccines

Anne Sophie Hatzfeld-Charbonnier^*,1, Audrey Lasek^*,1, Laurent Castera^*, Philippe Gosset, Thierry Velu, Pierre Formstecher^*, Laurent Mortier^*,2 and Philippe Marchetti^*,2,3

^* INSERM U837 Université de Lille 2, IFR114, CHRU et Unité de Thérapie Cellulaire, Faculté de Médecine 1, Lille, Cedex, France;
Department of Medical Oncology, Erasme Hospital, Université Libre de Bruxelles, Brussels, Belgium; and
U774, IFR17, Institut Pasteur de Lille, Lille, France

³ Correspondence: INSERM U837, 1 Place Verdun, F-59045, Lille Cedex, France. E-mail: philippe.marchetti{at}lille.inserm.fr

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-, 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- 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-3ß/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.

Key Words: heat shock • immunotherapy • temperature • hyperthermia • apoptosis • dendritic cells

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