Publications

Research Research groups Experimental immunology

About Experimental immunology

We study the immune system at the cellular and molecular level with a major focus on the plasma membrane organization of immune cells and cancer cells.

Research group leader

prof. dr. Annemiek van Spriel

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Aims

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Aims

The aim of our research group is to understand how plasma membrane organization governs immune cell function and how its disruption contributes to the development of cancer. The plasma membrane is not a uniform structure; instead, it is highly organized into dynamic protein assemblies that control signaling, cell–cell communication, and immune responses.While mounting evidence links altered membrane organization to cancer, the mechanisms by which changes in membrane architecture drive immune dysfunction and malignancy remain poorly defined.

Building on our discovery that specific membrane organizers protect against B cell lymphoma, our research focuses on elucidating how membrane protein networks shape immune signaling, cellular interactions, and tumor development. Ultimately, our goal is to define fundamental principles of membrane organization in the healthy immune system and in cancer, to improve immunotherapy.

Achievements

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Achievements

Our research aims to unravel the molecular mechanisms underlying tetraspanin function in immune cells and their role in malignant disease. By combining advanced imaging, signal transduction, molecular immunology, and preclinical models, we investigate how plasma membrane organization governs immune cell behavior in health and cancer.

Membrane organization of immune cells defines function. Our group defined how tetraspanin mediated membrane organization controls lymphocyte function, a concept synthesized in a Nature Reviews Immunology (2024) review. We demonstrated that CD37 and CD53 are essential for optimal B cell immunity (PLOS Pathogens, 2009; Science Signaling, 2012, 2017) and for effective T cell immunity (Cell Reports, 2022). Together, these studies establish tetraspanins as central organizers of immune cell signaling and function.
Identification of the biological function of CD20CD20 is a major therapeutic target in B cell malignancies and autoimmune diseases through the use of rituximab. Our group discovered that CD20 plays an essential biological role in immune synapse formation between B cells and T cells, revealing a previously unappreciated function beyond its clinical targeting (PNAS, 2025).
Tetraspanin CD37 protects against development of B cell lymphoma. We demonstrated that loss of the tetraspanin CD37 profoundly disrupts B cell homeostasis and leads to spontaneous B cell lymphoma development, identifying CD37 as a critical tumor suppressor in the B cell lineage. Furthermore, we showed that reduced CD37 expression correlates with poor clinical outcome in patients, establishing its prognostic value. These findings, reported in Journal of Clinical Investigation (2016), Blood (2019), and Blood Advances (2022), link CD37 mechanistically and clinically to lymphomagenesis.
Fatty acid metabolism drives lymphomagenesis. Our research uncovered fatty acid metabolism as a key driver of B cell lymphoma development, revealing a previously unrecognized metabolic dependency of malignant B cells. We showed that lymphoma cells rewire lipid metabolic pathways to support growth and survival, highlighting fatty acid metabolism as a promising therapeutic target (Nature Communications, 2022; Cellular & Molecular Immunology, 2020).
Advanced imaging and proteomics of the immune cell surface. We pioneered a conceptual and visual model of the tetraspanin web on immune cells by applying super resolution microscopy to map its nanoscale organization. This work provided new insight into how tetraspanins structurally organize immune receptors at the plasma membrane and was published in Scientific Reports (2015), Biophysical Journal (2024), and Journal of Biological Chemistry (2024), Molecular Oncology (2026).Building on this body of work, we now investigate how insights into membrane organization can be leveraged to improve antibody based cancer immunotherapy, with the goal of enhancing efficacy while increasing tumor specificity.