PD-1 blockade mitigates surgery-induced immunosuppression and increases the efficacy of photodynamic therapy for malignant pleural mesothelioma

Surgical resection can influence tissue behavior and immune interactions, leading to an altered inflammatory state. Our clinical trial delivers intraoperative photodynamic therapy (PDT) to the thoracic cavity after macroscopic complete resection of malignant pleural mesothelioma (MPM) tumors. We have previously published evidence of systemic inflammation via increases in circulating levels of IL-6 after surgical resection. Thus, we expect surgery to alter local signal transduction in the resection field by the time that PDT is delivered. To detect these signaling changes, RNA sequencing analysis was performed on tumor tissue isolated at different time intervals during the surgery (and prior to PDT) from 33 MPM patients. We discovered several pathways associated with tumor behavior and immune function were activated over the course of surgery.