Multiplex imaging of lymph nodes: How Euro-BioImaging is advancing cancer research through the canSERV funding

The immune system plays an important role in fighting cancer but can also be a pathway of metastasis - therefore understand the interactions of the immune system, including the lymph system. Lymphatic endothelial cells are an integral part of the lymph node, delineating the lumen of all nodal lymphatic sinuses. Consequently, lymph node and lymphatic endothelial cells are crucial for immunity as they regulate lymph flow, control access of antigens from the afferent lymph, and influence immune cell migration to and from the lymphatic sinuses. They also directly regulate immune cell activation and survival. Through these functions, certain lympthatic endothelial cells in special regions of the lymph node are activated in cancer. It remains an open question how these cells' activities and the interactions of the endothelial cells with immune cells work and how they differ in healthy, tumor-draining, and metastatic lymph nodes. These questions have important implications for tumor immunity and immunotherapy responsiveness.

Dr. Sarah Hofmann, a postdoctoral researcher in Prof. Dr. Lothar Dieterich’s lab at the University Hospital Mannheim, is looking at address exactly these questions systematically using well-characterized models of checkpoint-sensitive and -resistant melanoma in mice. This will offer groundbreaking insights into cancer-related mechanisms and advance the development of bioengineered strategies for combating cancer.

Sarah’s story: Exploring immune responses in lymph nodes

Dr. Sarah Hofmann is studying the lymphatic system, with a specific focus on lymph nodes. Her work delves into how the immune response is regulated within the lymph node, particularly in the context of tumour draining environments and the differences between that and healthy tissue.

Sarah received funding from the canSERV project (Horizon Europe GA No. 101058620) to use Euro-BioImaging's research facilities to further elucidate the spatial mapping of lymphatic endothelial and immune cell interactions in tumor-draining lymph nodes. Thanks to this funding, Sarah was able to get access to state-of-the-art multiplex-capable microscopes provided by Euro-BioImaging's EMBL Node at the EMBL Imaging Centre in Heidelberg. This powerful technique allows her to visualise more than five different markers simultaneously in a single sample, providing a richer and more detailed understanding of the complex cellular interactions at play.

During the first of a number of visits to the EMBL Imaging Centre, Sarah accessed the Leica STELLARIS platform capable of performing 15-colour multiplex imaging which enabled her and her team to investigate the spatial relationship between lymph nodes and lymphatic endothelial cells subtypes and selected immune cell populations and activation states and more precisely mapping the positioning of multiple immune cell subtypes relevant for tumor immunity, including rare populations such as innate lymphoid cells. Sarah’s prior experience as an Applications Specialist at Leica, where she focused on multiplexing techniques, made her aware of the power of this imaging technology. 

I am very grateful to have access to the Euro-BioImaging EMBL Node. This was the only opportunity for me to do experiments using the STELLARIS microscopes. I can highly recommend everybody to apply for funding, and take advantage of the excellent systems available here.
Sarah Hofman, University Hospital Mannheim

Imagine Technologies for Cancer Research: how Euro-BioImaging is contributing to reaching an understanding of cancer

Advanced imaging instruments, such as multiplex-capable microscopes used in this canSERV project, hold significant potential to transform our understanding of cancer and ability to fight it by enabling high-resolution spatial mapping of complex cellular interactions within the tumor microenvironment and associated lymphoid organs, thus enabling researchers to uncover previously unrecognized patterns of cellular crosstalk and lymph node organization that underpin tumor progression. Such insights are necessary for identifying novel therapeutic targets aimed at restoring lymph node immune function, enhancing tumor immunity, and improving the efficacy of immunotherapies, thus directly advancing the goal of reaching a deeper, more integrated understanding of cancer and fighting it.

Euro-BioImaging, as a leading European research infrastructure, plays a vital role in accelerating research topics such as cancer by democratising the access to cutting-edge imaging technologies, expertise, and training across its large and diverse network of imaging facilities. By offering researchers access to state-of-the-art imaging modalities, Euro-BioImaging enables comprehensive visualization and analysis of complex biological systems at cellular, subcellular, tissue, and organism resolutions, thus contributing to the overarching mission of initiatives like the Cancer Grand Challenge and EU Mission Cancer to deepen our understanding of cancer biology and develop more effective therapeutic strategies.

The canSERV project, funded by the European Union under Horizon Europe, provides critically needed funding to allow researchers to access services and expert support from Euro-BioImaging and many other Research Infrastructures to advance their cancer research.

Article written by Ayoub El Ghadraoui