Introduction Tumor Treating Fields (TTFields) are a clinically applied anti-neoplastic treatment modality delivered via noninvasive application of low intensity (1-3 V/cm), intermediate frequency (100-500 kHz), alternating electric fields. In this study we evaluated the effects of in vitro TTFields application on dendritic cell (DC) properties that include maturation, phagocytosis, and migration.
Methods Bone marrow cells were flushed from the femurs and tibias of 5-7 week old C57BL/6 mice to generate bone marrow-derived DCs. For the DC maturation assay, TTFields treated cancer cells were added at a ratio of 1:1 for 24 h. DC maturation was analyzed using flow cytometry to assess surface expression of major histocompatibility complex class II (MHC II), CD40, and CD80 activation markers. For the phagocytosis assay, CellTrackerTM Deep Red Dye, pre-stained TTFields treated cancer cells were added at a ratio of 1:1 for 2h and phagocytosis by DCs was evaluated using flow cytometry. DC migration assays were performed using a modified Matrigel coated Boyden chamber either with or without C-C Motif Chemokine Ligand 19 (CCL19), utilized as a chemoattractant.
Results TTFields treated cancer cells were effectively phagocytosed by DCs, while untreated control cells did not show similar outcomes. In addition, activation markers were found to be upregulated in DCs that were co-cultured with TTFields treated cells. This up-regulation was observed for all the costimulatory molecules analyzed. DC migration assays, showed no significant difference in migration rates between untreated and TTFields treated DCs, with or without the chemoattractant CCL19.
Conclusions These in vitro results indicate that TTFields treated cancer cells promote DC elicited phagocytosis and DC maturation. Moreover, in contrast to previous studies reporting that TTFields show an inhibitory effect on cancer cell migration, we demonstrate that TTFields do not impair the migratory properties of DCs.
Citation Format: Tali Voloshin, Shiri Davidi, Noa Kaynan, Rosa Schneiderman, Alexandra Volodin, Moshe Giladi, Uri Weinberg, Yoram Palti. Effects of tumor treating fields (TTFields) on dendritic cells functionality [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 6662.