Studying the influence of macrophage receptors on macrophage activation depending on different growth patterns of colorectal liver metastases

• Applicant: Dr. Karl Knipper
• Subject Area: Gastroenterology ; Hematology, Oncology
• Term: since 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 564937880

Despite several treatment options, the survival of patients with colorectal liver metastases is short. The introduction of immune checkpoint inhibitors improved the treatment of various tumor entities. While these inhibitors are mainly focused on the interaction with T cells, treatment options centered on macrophages are still pending. Several growth patterns of colorectal liver metastases exist. These growth patterns differ in prognosis and angiogenesis. Additionally, the distribution of resident and nonresident macrophages is dissimilar. Furthermore, genes associated with inflammation are overexpressed in metastases with desmoplastic growth patterns. In contrast, genes involved in cell proliferation are overexpressed in metastases with replacement growth patterns. The primary goal of this project is to identify a macrophage receptor that is crucial for macrophage activation and differentiation depending on the histopathological growth pattern. Inhibition of this macrophage receptor could potentially lead to changed tumor cell proliferation, growth pattern, and activation of fibroblasts or T cells. The secondary goal is the general characterization of macrophage activation in colorectal liver metastases depending on the histopathological growth pattern. Therefore, spatial, single-cell transcriptomics will be performed on human liver metastasis samples. Here, potential receptors should be identified. The interaction of the 30 most promising receptors will be examined in vivo using a CRISPR screening method in a colorectal liver metastases mice model. Consecutively, the receptor with the highest potential will be solely inhibited. Here, we will examine the influence of inhibition of this receptor on tumor progress, growth pattern, and the tumor microenvironment.

• DFG Programme: WBP Fellowship
• International Connection: Belgium
• Hosts: Professor Martin Guilliams, Ph.D.; Professorin Dr. Sabine Tejpar