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

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 anti-tumor 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 sub-lethal heat shocks throughout the generation of DC. Using this protocol, we observed that heat stress did not perturb either () the morphology and 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 TNFα, 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 a mixed allogeneic lymphocyte reaction. Interestingly, heat stress enhanced the migratory capacities of DC in response to MIP3β/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.