PT - JOURNAL ARTICLE AU - Theurich, S AU - Becker, HJ AU - Wennhold, K AU - Schlösser, H AU - Marbach, F AU - Garcia-Marquez, M AU - Shimabukuro-Vornhagen, A AU - Schreml, J AU - von Bergwelt-Baildon, M TI - P03.16 Functional defects in B-cells of patients with von-Hippel-Lindau Syndrome AID - 10.1136/jitc-2020-ITOC7.55 DP - 2020 Oct 01 TA - Journal for ImmunoTherapy of Cancer PG - A29--A29 VI - 8 IP - Suppl 2 4099 - http://jitc.bmj.com/content/8/Suppl_2/A29.1.short 4100 - http://jitc.bmj.com/content/8/Suppl_2/A29.1.full SO - J Immunother Cancer2020 Oct 01; 8 AB - 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).Disclosure Information 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.