Michael von Bergwelt-Baildon - assoc. RG

Function of B cells in tertiary lymphoid structures in pancreatic tumors


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.
Specific aim 1: Deciphering the role of B cells in anti-tumor immune responses of TLS in murine pancreatic adenocarcinoma.
Specific aim 2:  Identification of soluble and cellular factors influencing TLS-formation in the tumor microenvironment of two pancreatic adenocarcinoma models.
Specific aim 3: Defining TLS in human pancreatic cancer

Clinical/medical relevance and sustainability in disease understanding

TLS reflect an ongoing anti-tumor immune response and thus are of great interest as biomarkers for immune interventions. Furthermore, induction of TLS and transfer of single cellular TLS components both merit detailed analysis concerning their potential role as therapeutic approaches in advanced pancreatic cancer.

Prof. Dr. med. Dr. rer. nat. Michael von Bergwelt-Baildon

Dept. I of Internal Medicine / RG location - Building 16

Prof. Dr. med. Dr. rer. nat. Michael von Bergwelt-Baildon

assoc. CMMC Research Group


Publications - Michael von Bergwelt-Baildon

Link to PubMed

Cd20+ B cells organized in a tertiary lymphoid structure in gastric cancer
Cd20+ B cells = red, cd3+ T cells = green, nuclei = blue
(Schlößer et al. 2016)