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

Journal of Leukocyte Biology

Audrey Lasek¹  Laurent Castera¹  Philippe Gosset³  Laurent Mortier¹  Thierry Velu²  Anne Sophie Hatzfeld-Charbonnier¹  Philippe Marchetti¹  Pierre Formstecher¹ 

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

关键词: heat shock;    immunotherapy;    temperature;    hyperthermia;    apoptosis;    dendritic cells;   

DOI  :  10.1189/jlb.0506347

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

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-α, 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-γ 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-3β/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.

【 授权许可】

Unknown