Research group Experimental immunology

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

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

  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 biological function of CD20CD20

  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

  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

  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 immune cell surface

  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.

Publications

See the publication list of the research group leader on Web of Science.

• A selection of our publications

  • Cell surface interactome analysis identifies TSPAN4 as a negative regulator of PD-L1 in melanoma. Franken GA, Abel Gutierrez A, van Rossum I, Spruijt CG, Vermeulen M, van Mierlo G, Scheijen B, van Spriel AB. Mol Oncol. 2026 May;20(5):1140-1160. doi: 10.1002/1878-0261.70182
  • Decoding the immune-tumor synapse for data-driven design of next-generation immunotherapies. van Rossum ISC, van Spriel AB, van Mierlo G. Trends Immunol. 2026 Mar 17:S1471-4906(25)00317-5. doi: 10.1016/j.it.2025.12.009.
  • CD70 recruitment to the immunological synapse is dependent on CD20 in B cells. Arp AB, Abel Gutierrez A, Ter Beest M, Franken GA, Warner H, Rodgers Furones A, Kenyon AN, Jäger F, Cabrera-Orefice A, Kläsener K, van Deventer S, Droesen L, Dunlock VME, Classens R, Staniek J, Borst J, Reth M, Brandt U, Gros P, Kuijpers TW, Heemskerk MHM, Rizzi M, Querol Cano L, van Spriel AB. Proc Natl Acad Sci U S A. 2025 Apr 22;122(16):e2414002122. doi: 10.1073/pnas.2414002122
  • The conformation of tetraspanins CD53 and CD81 differentially affects their nanoscale organization and interaction with their partners. Schwerdtfeger F, Hoogvliet I, van Deventer S, van Spriel AB. J Biol Chem. 2024 Sep;300(9):107685. doi: 10.1016/j.jbc.2024.107685.
  • Membrane organization by tetraspanins and galectins shapes lymphocyte function. Querol Cano L, Dunlock VE, Schwerdtfeger F, van Spriel AB. Nat Rev Immunol. 2024 Mar;24(3):193-212. doi: 10.1038/s41577-023-00935-0.
  • Fatty acid metabolism in aggressive B-cell lymphoma is inhibited by tetraspanin CD37. Peeters R, Cuenca-Escalona J, Zaal EA, Hoekstra AT, Balvert ACG, Vidal-Manrique M, Blomberg N, van Deventer SJ, Stienstra R, Jellusova J, Giera M, Hannibal L, Spiekerkoetter U, Ter Beest M, Berkers CR, van Spriel AB. Nat Commun. 2022 Sep 13;13(1):5371. doi: 10.1038/s41467-022-33138-7.
  • Tetraspanin CD53 controls T cell immunity through regulation of CD45RO stability, mobility, and function. Dunlock VE, Arp AB, Singh SP, Charrin S, Nguyen V, Jansen E, Schaper F, Beest MT, Zuidscherwoude M, van Deventer SJ, Nakken B, Szodoray P, Demaria MC, Wright MD, Querol Cano L, Rubinstein E, van Spriel AB. Cell Rep. 2022 Jun 28;39(13):111006. doi: 10.1016/j.celrep.2022.111006.
  • IRF8 is a transcriptional activator of CD37 expression in diffuse large B-cell lymphoma. Elfrink S, Ter Beest M, Janssen L, Baltissen MP, Jansen PWTC, Kenyon AN, Steen RM, de Windt D, Hagemann PM, Hess C, van Spronsen DJ, Hoevenaars B, van der Spek E, Xu-Monette ZY, Young KH, Kaffa C, Bervoets S, van Heek J, Hesius E, de Winde CM, Vermeulen M, van den Brand M, Scheijen B, van Spriel AB. Blood Adv. 2022 Apr 12;6(7):2254-2266. doi: 10.1182/bloodadvances.2021004366.
  • High frequency of inactivating tetraspanin CD37 mutations in diffuse large B-cell lymphoma at immune-privileged sites. Elfrink S, de Winde CM, van den Brand M, Berendsen M, Roemer MGM, Arnold F, Janssen L, van der Schaaf A, Jansen E, Groenen PJTA, Eijkelenboom A, Stevens W, Hess CJ, van Krieken JH, Vermaat JSP, Cleven AHG, de Groen RAL, Neviani V, de Jong D, van Deventer S, Scheijen B, van Spriel AB. Blood. 2019 Sep 19;134(12):946-950. doi: 10.1182/blood.2019001185. Epub 2019 Jul 31.
  • Tetraspanin CD37 protects against the development of B cell lymphoma. de Winde CM, Veenbergen S, Young KH, Xu-Monette ZY, Wang XX, Xia Y, Jabbar KJ, van den Brand M, van der Schaaf A, Elfrink S, van Houdt IS, Gijbels MJ, van de Loo FA, Bennink MB, Hebeda KM, Groenen PJ, van Krieken JH, Figdor CG, van Spriel AB. J Clin Invest. 2016 Feb;126(2):653-66. doi: 10.1172/JCI81041.