Longitudinal Modulation of Loco-Regional Immunity in Ovarian Cancer Patients Receiving Intraperitoneal Chemotherapy

SIMPLE SUMMARY: Insight into how immune cells change during chemotherapy can help develop new ways to support immune function and maximize treatment success in epithelial ovarian cancer (EOC). We aim to define the impact of chemotherapy on the tumor immune microenvironment by studying changes in immune-related gene expression and proteins within fluid that surrounds EOC. By testing different time points during chemotherapy, we can gain insight into the interplay between immune cells and cancer cells. Longitudinal profiling of cellular and molecular changes in immune surveillance during treatment of ovarian cancer will help find more effective combination treatments that can improve outcomes in EOC. ABSTRACT: The immune tumor microenvironment (TME) of epithelial ovarian cancer (EOC) carries both effector and suppressive functions. To define immune correlates of chemotherapy-induced tumor involution, we performed longitudinal evaluation of biomarker expression on serial biological specimens collected during intraperitoneal (IP) platinum-based chemotherapy. Serial biological samples were collected at several time points during IP chemotherapy. RNA from IP fluid cells and tumor tissue was analyzed via NanoString. Meso Scale Discovery (MSD) multiplex assay and ELISA for MUC1 antibodies were performed on plasma and IP fluid. Differentially expressed genes in IP fluid demonstrate an upregulation of B cell function and activation of Th2 immune response along with dampening of Th1 immunity during chemotherapy. MSD analysis of IP fluid and gene expression analysis of tumor tissue revealed activation of Th2 immunity and the complement system. Anti-MUC1 antibodies were detected in IP fluid samples. IP fluid analysis in a secondary cohort also identified chemotherapy-induced B cell function genes. This study shows that serial IP fluid sampling is an effective method to capture changes in the immune TME during chemotherapy and reveals treatment induced changes in B cell function and Th2 immunity.