Tumor Treating Fields inhibit cell proliferation and promote immunogenic cell death in biliary tract cancer cells

Tumor Treating Fields (TTFields) are low-intensity, intermediate-frequency alternating electric fields that exert antimitotic effects on cancer cells. This study evaluated the in vitro efficacy of TTFields on biliary tract cancer (BTC) cell lines HCCC-9810 and RBE, investigating their sensitivity to TTFields across varying frequencies and electric field intensities. The results demonstrated that a frequency of 150 kHz induced the most pronounced cytotoxic effects, significantly impairing clonogenicity and migratory capacity while inducing abnormal mitotic processes. Furthermore, TTFields treatment triggered a marked upregulation of immunogenic cell death (ICD) biomarkers, including enhanced surface exposure of calreticulin (CRT) and increased extracellular release of high mobility group box 1 (HMGB1) and ATP. These findings indicate that TTFields represent a promising therapeutic approach for BTC, not only by suppressing tumor proliferation but also by enhancing ICD.