P03.16 Functional defects in B-cells of patients with von-Hippel-Lindau Syndrome

• Published in: Journal for immunotherapy of cancer Vol. 8; no. Suppl 2; p. A29
• Main Authors: Theurich, S, Becker, HJ, Wennhold, K, Schlösser, H, Marbach, F, Garcia-Marquez, M, Shimabukuro-Vornhagen, A, Schreml, J, M von Bergwelt-Baildon
• Format: Journal Article
• Language: English
• Published: London BMJ Publishing Group LTD 01-10-2020
• Subjects: Antigens; Gene expression; Immunotherapy; Mutation
• ISSN: 2051-1426
• DOI: 10.1136/jitc-2020-ITOC7.55

Von-Hippel-Lindau (VHL)-disease is an inherited cancer syndrome characterized by a variety of benign and malignant tumors, which develop upon mutation of the second allele of the VHL-tumor suppressor gene. The VHL-protein (pVHL) regulates hypoxia-induced transcription factors (Hif) and by this plays a central role for metabolic cellular adaptations to hypoxic conditions. VHL/Hif regulation plays a well-established role in the development and function of immune cells and already VHL-haploinsufficiency can alter gene expression patterns. In contrast, little is known about primary immune cell functions in VHL-patients. In this study, we analyzed the functional capacity of CD40-stimulated B-cells to act as antigen-presenting cells. We confirmed mono-allelic VHL-gene mutations in B-cells from thirteen VHL-patients and found that their response to CD40-stimulation was significantly reduced. On a functional level this translated to an impaired ability to act as antigen presenting cells leading to impaired T-cell responses in vitro. Taken together, we demonstrate that VHL-haploinsufficiency deregulates B-cell functions following CD40-activation as a new aspect of VHL-syndrome. (The study was registered in the German Clinical Trial Registry (www.drks.de); ID: DRKS00012413).S. Theurich: B. Research Grant (principal investigator, collaborator or consultant and pending grants as well as grants already received); Modest; Verein VHL (von Hippel-Lindau) betroffener Familien e.V.. H.J. Becker: None. K. Wennhold: None. H. Schlösser: None. F. Marbach: None. M. Garcia-Marquez: None. A. Shimabukuro-Vornhagen: None. J. Schreml: None. M. von Bergwelt-Baildon: None.