Researcher Database
Prof. Dr. Dr. Michael von Bergwelt
Medizinischen Klinik und Poliklinik III
Marchioninistr. 15
81377 München
Program
Clinical Communication Platform (CCP)
Summary
The breakthrough therapeutic efficacy of immune checkpoint inhibitors underlines the central role of the immune system in cancer. Infiltration of lymphocytes has been shown to either exhibit an inhibitory or enhancing effect on tumor growth. Especially the role of tumor-infiltrating B cells is complex. B cells serve many immunological functions including antigen-presentation, antibody-secretion, direct toxicity, cytokine secretion, but also immune inhibition. Whether B cells promote or inhibit tumor growth seems to depend on a number of variables such as tumor type, stage and the dominating B cell subset. However, a high density of T and B cells in the tumor microenviroment is correlated with increased patient survival in several types of cancer. For many years, it was assumed that an adaptive anti-tumor immune response is elicited not in the tumor itself, but in secondary lymphoid organs (SLO). However recently, increasing evidence suggests that anti-tumor immune reactions may also be generated in the tumor microenvironment in so called tertiary lymphoid structures (TLS). These TLS display an overall structure similar to that of SLOs with predominant B-cell rich areas surrounded by specialized blood vessels, i.e. high endothelial venules, and T-cell rich areas that contain clusters of T cells and mature dendritic cells. However, the role of cellular components on TLS formation or the function of lymphocytes in TLS of cancer patients is still not well understood.
Our work focuses on in-depth analysis of TLS/B-cell immunity in cancer and the identification of novel, functionally defined B cell subsets. Based on these basic research activities our group develops B cell targeted immune therapies.
a) Targeting of regulatory B cells in the TME (Type-II antibodies, TLR-9 agonists, CART, kinase inhibitors)
b) Adoptive transfer of tumor-antigen specific B cells (Dual approach: plasma cells plus CD40- activated B cells)
Secondary focuses of our work are combination immunotherapies, immune escape and cancer immune metabolics.
To translate these activities consequently and successfully into clinical trials we are operating our own IIT/Ph1 immunotherapy and immune monitoring program at the Universities of Munich and Cologne.
DKTK Junior Group Leader for Cancer Systems Biology
Single-cell approaches have not only revealed a wide variety of cell states, characterized by cells exhibiting striking differences in their transcriptional profile, but have also illuminated the mechanisms underlying state transitions in health and disease. Cellular plasticity and adaptive state changes have recently emerged as a basis for therapeutic resistance in cancer, and a better understanding of how cell state transitions are regulated is critical to develop therapeutic approaches that can overcome therapy resistance.
Our research focuses on understanding the mechanisms driving non-genetic cellular heterogeneity and therapy resistance in malignancy. Using novel single-cell sequencing approaches, we seek to develop new experimental and computational strategies to define altered cell states in both, cancer and immune cells. Our aim is to leverage a data driven strategy combined with single cell genomics and systems biology to address the challenges posed by heterogeneity in cancer, and to develop new strategies to overcome it, with the aim of translating laboratory-based findings into the clinic.