Organic Electrochemical Transistors for Real-Time Detection of Immune System Early Activation during Atezolizumab-Bevacizumab Treatment in Hepatocellular Carcinoma

: Poly(3,4-ethylenedioxythiophene):polystyrenesulfonate (PEDOT:PSS)-based organic electrochemical transistors (OECTs) have been demonstrated as versatile biosensors in recent years. Owing to the biocompatibility and chemical stability of the organic mixed ionic and electronic conductor in cell media, they allow real-time, in vitro electrical monitoring of cell lines, providing quantitative outcomes of their health status. Here, we propose and validate a sensitive OECT device for direct in vitro monitoring of peripheral blood mononuclear cell (PBMC) activity in a coculture assay. PBMCs from patients with advanced hepatocellular carcinoma (HCC) responding and nonresponding to atezolizumab (anti-PD-L1) and bevacizumab (anti-VEGF) are cocultured with Huh7 and SNU449 HCC cell lines directly grown onto OECTs. A strong correlation between the OECT electrical response, standard cell growth, death assays, and IL6 levels is observed, which is confirmed for cocultures involving PBMCs from healthy controls and patients treated with immunosuppressive drugs (namely, positive and negative controls, respectively). Our low-cost and scalable device has the potential to detect PBMC activation induced by atezolizumab-bevacizumab in the very early stages of HCC treatment, allowing for nonresponders' inclusion in alternative treatments. This approach might be of great interest to several human cancers treated with immune checkpoint inhibitors (ICIs), providing sensitive, automated, and noninvasive tools to complement clinical practice.