1. Influence of heat stress on human monocyte-derived dendritic cell functions with immunotherapeutic potential for antitumor vaccines
- Author
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Pierre Formstecher, Thierry Velu, Audrey Lasek, Anne Sophie Hatzfeld-Charbonnier, Laurent Mortier, Laurent Castera, Philippe Gosset, Philippe Marchetti, Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U1172 Inserm - U837 (JPArc), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Lille Nord de France (COMUE)-Université de Lille, Biomolécules et inflammation pulmonaire, Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé, Department d'oncologie médicale [Bruxelles, Belgique], Hôpital Erasme [Bruxelles] (ULB), Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB)-Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), This work was supported by grants from the Ligue Contre le Cancer (Comité du Nord, to P. M.), the Société Française de Dermatologie (to P. M.), and the Cancéropole Nord Ouest. A. S. H‐C. and L. C. received fellowships from the Cancéropole Nord Ouest and the Fondation pour la Recherche Médicale, Respectively. Drs. Carolyn Straehle and Catherine Duez are gratefully acknowledged for helpful comments, Hatzfeld-Charbonnier, Anne-Sophie, Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 (JPArc), and Université Lille Nord de France (COMUE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille
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Lipopolysaccharides ,MESH: Interleukin-12/metabolism ,MESH: Chemokine CCL19 ,T-Lymphocytes ,medicine.medical_treatment ,Monocytes ,MESH: Chemokines, CC/immunology ,MESH: Structure-Activity Relationship ,0302 clinical medicine ,Cell Movement ,Immunology and Allergy ,MESH: Th1 Cells/immunology ,0303 health sciences ,apoptosis ,MESH: Monocytes/immunology ,MESH: Th1 Cells/drug effects ,hyperthermia ,Interleukin-12 ,heat shock ,Cell biology ,Phenotype ,Cytokine ,Chemokines, CC ,030220 oncology & carcinogenesis ,Interleukin 12 ,[SDV.IMM]Life Sciences [q-bio]/Immunology ,immunotherapy ,MESH: Heat-Shock Response/immunology ,Hyperthermia ,[SDV.IMM] Life Sciences [q-bio]/Immunology ,MESH: Cell Survival/immunology ,Cell Survival ,MESH: Apoptosis/immunology ,MESH: Lipopolysaccharides/pharmacology ,MESH: Tumor Necrosis Factor-alpha/metabolism ,MESH: T-Lymphocytes/drug effects ,Immunology ,MESH: Cell Movement/immunology ,Biology ,MESH: Cancer Vaccines/immunology ,MESH: Phenotype ,Cancer Vaccines ,Article ,Structure-Activity Relationship ,03 medical and health sciences ,Immune system ,Antigen ,MESH: T-Lymphocytes/immunology ,medicine ,Humans ,dendritic cells ,Heat shock ,030304 developmental biology ,MESH: Humans ,Tumor Necrosis Factor-alpha ,MESH: Immunotherapy ,temperature ,Cell Biology ,Immunotherapy ,Dendritic cell ,Th1 Cells ,medicine.disease ,Chemokine CCL19 ,Heat-Shock Response ,MESH: Dendritic Cells/immunology - 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-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.
- Published
- 2007
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