Targeting the tumor microenvironment to improve cancer immunotherapy

Ovarian cancer is usually diagnosed at an advanced stage due to the absence of early clinical symptoms. Most patients develop recurrence after first-line treatment, emphasizing the need for alternative treatment strategies. However, immunotherapeutic approaches have shown limited success in clinical trials thus far. This suggests that the tumor microenvironment, and especially certain types of immune cells, may counteract successful antitumor immunity. 

Recently, neutrophils have been identified as major players in limiting the efficacy of T cell-based immunotherapies in a variety of solid cancer models. Advanced stage ovarian cancer is typically associated with peritoneal carcinomatosis and malignant ascites, which represents a special type of microenvironment. However, the mechanism by which neutrophils and other subtypes of myeloid immune cells contribute to immune regulation and disease progression is poorly understood. Therefore, this project aims to provide a deeper understanding of neutrophil pathobiology in ovarian cancer using preclinical models and clinical samples. The long-term goal of our research is to identify novel targeted and personalized treatment strategies focusing on reprogramming the tumor mircroenvironment in combination with immunotherapy that may help to improve the treatment of advanced stage ovarian cancer patients.