o:25429 Plasma-activated medium potentiates the immunogenicity of tumor cell lysates for dendritic cell-based cancer vaccines Medijum aktiviran plazmom pojačava imunogenost lizata tumorskih ćelija za vakcine protiv raka bazirane na dendritskim ćelijama en ABSTRACT Autologous dendritic cells (DCs)-based vaccines are considered quite promising for cancer immunotherapy due to their exquisite potential to induce tumor antigen-specific cytotoxic T cells. However, a lack of efficient protocols for inducing immunogenic tumor antigens limits the efficacy of DC-based cancer vaccines. Here, we found that a plasma-activated medium (PAM) induces immunogenic cell death (ICD) in tumor cells but not in an immortalized L929 cell line or human peripheral blood mononuclear cells. PAM induced an accumulation of reactive oxygen species (ROS), autophagy, apoptosis, and necrosis in a concentration-dependent manner. The tumor lysates prepared after PAM treatment displayed increased immunogenicity in a model of human monocytederived DCs, compared to the lysates prepared by a standard freezing/thawing method. Mature DCs loaded with PAM lysates showed an increased maturation potential, as estimated by their increased expression of CD83, CD86, CD40, IL-12/IL-10 production, and attenuated PDL1 and ILT-4 expression, compared to the DCs treated with control tumor lysates. Moreover, in co-culture with allogeneic T cells, DCs loaded with PAM-lysates increased the proportion of cytotoxic IFN- + granzyme A+ CD8+ T cells and IL-17A producing T cells and preserved the Th1 response. In contrast, control tumor lysates-treated DCs increased the frequency of Th2 (CD4+IL-4+), CD4, and CD8 regulatory T cell subtypes, none of which was observed with DCs loaded with PAM-lysates. Cumulatively, these results suggest that the novel method for preparing immunogenic tumor lysates with PAM could be suitable for improved DC-based immunotherapy of cancer patients. plasma activated medium, dendritic cells, tumor vaccines, Th polarization 1552099 10.3390/cancers13071626 2022-05-17T09:00:39.873Z 44 yes 46 Sergej Tomić University of Belgrade, Institute for the Application of Nuclear Energy INEP, Serbia doktor bioloških nauka 0000-0003-2570-1295 Miodrag Čolić University of Belgrade, Institute for the Application of Nuclear Energy INEP, Serbia akademik person Zoran Lj. Petrović Serbian Academy for Sciences and Arts, Belgrade, Serbia person Marina Bekić University of Belgrade, Institute for the Application of Nuclear Energy INEP, Serbia person 0000-0002-6945-4241 Nikola Škoro University of Belgrade, Institute of Physics, Serbia person Nevena Puač University of Belgrade, Institute of Physics, Serbia person Anđelija Petrović University of Belgrade, Institute of Physics, Serbia person application/pdf 3272204 https://phaidrabg.bg.ac.rs/o:25429 no yes 16 70 92000001 11A29 11A2904 11A23 Cancers 13 7 2021