Research Group Jenny Kienzler

Keywords

Malignant brain tumors, immune suppressive microenvironment, immunotherapy, tumor associated macrophages, tissue-specific vs. recruited immune responses

Summary & Mission statement

Our group studies how myeloid cells – and in particular tumor-associated macrophages – control the immunosuppressive microenvironment in malignant brain tumors, aiming to develop novel immunotherapies that significantly improve survival outcomes and quality of life for patients with glioblastoma and brain metastases.

Overview

Malignant brain tumors present a unique immunological challenge, harboring some of the most immunosuppressive microenvironments in oncology. Despite the transformative success of immunotherapies across cancer types, glioblastoma and brain metastases remain largely refractory to these approaches, with patients facing median survivals of 15 months and less than one year, respectively. This resistance stems from the profound immunosuppression orchestrated by tumor-associated macrophages that dominate the brain tumor microenvironment.

Macrophages in brain tumors represent a complex population comprising both tissue-resident microglia and invading monocyte-derived cells. Far from being a homogeneous immunosuppressive population, we find that these myeloid subsets exhibit distinct ontological origins, spatial distributions, and functional properties that differ markedly between primary glioblastoma and brain metastases. Our group investigates the mechanisms governing macrophage polarization and trafficking in brain tumors, and how these processes can be therapeutically manipulated to restore antitumor immunity.

Current research projects in our lab include: 1. High-dimensional cellular profiling to identify novel therapeutic targets and biomarkers 2. Cytokine pathway manipulation to reprogram immune cell function 3. Genetic and pharmacological approaches to understand specialized macrophage populations in tumor progression. Our overall objective is to develop targeted interventions that reshape the tumor immune microenvironment to enhance therapeutic efficacy.

Integration of human samples and tumor explants from malignant brain tumors, with in vivo testing using immunocompetent glioblastoma and brain metastasis mouse models.