prof. Sophie Janssens (PhD)

My research team aims to understand how dendritic cells decode tumor antigens. By safeguarding the balance between immunity and tolerance, dendritic cells play a pivotal role in the anti-tumor immune response by orchestrating how our immune system will react to the tumor. As antigen presenting cells, they continuously patrol the environment for antigens, also in the tumor microenvironment where they take up dying tumor cells. Once they have taken up an antigen, they mature, migrate to the T cells in the lymph nodes and present the antigens. Depending on how dendritic cells perceive the antigen at the time of uptake, -as dangerous or as self-, they will instruct our adaptive immune system to kill or tolerate the tumor. This will lead to tumor rejection or tumor growth, respectively. How dendritic cells decode tumor antigens and what determines the balance between immunity and tolerance remains poorly understood. Our lab addresses how the uptake of dying cells induces tolerogenic versus immunogenic dendritic cell maturation. We recently uncovered a key role for cholesterol metabolic pathways at this decision point. As a proof of concept, we found approaches to affect the maturation of DCs (amongst others) in the tumor by targeting them in vivo with modified lipid nanoparticles, resulting in immunogenic presentation of tumor antigens. Future studies in my lab aim to unravel what defines the type of dendritic cell maturation within the tumor microenvironment and how we can manipulate this to enforce tumor rejection.
 

Dr. Sophie Janssens received her Master in Biology at the University of Antwerp and her PhD in Sciences at Ghent University (2003), where she studied the role of MyD88 in innate immune signaling. She went for her postdoc to the lab of Prof. J. Tschopp at the University of Lausanne (2005) to work on the PIDDosome and cell fate decisions upon DNA damage. After a second postdoc at the University of Antwerp, she became Full Professor at Ghent University to coordinate a novel research line on ER stress and inflammation (2011).
Her research team focuses on the role of the unfolded protein response in immune cells. They discovered that one subset of conventional dendritic cells shows a particular high activation of the IRE1/XBP1 branch in steady state. This does not lead to the activation of a canonical UPR response but appeared linked to their homeostatic maturation process. These insights brought them into the field of DC maturation and signaling pathways steering immunogenic versus tolerogenic maturation. They uncovered an essential role for cholesterol metabolism at the crossroads between immunity and tolerance, with important implications for tumor immunology. Recent projects in the Lab aim to map pathways driving dendritic cell maturation within the tumor environment and assess in vivo approaches to affect the maturation program and redirect the adaptive immune outcome versus tumor rejection. Prof. Janssens’ work is supported by an ERC consolidator grant (DC-RIDDLE).
 

• prof. Sophie Janssens (PhD) - principal investigator, full professor
• dr. Jessica Vetters (PhD) - post-doctoral fellow
• Sofie Rennen - doctoral fellow
• Karo Van Lil - doctoral fellow
   

• Decoding immunogenic cell death from a dendritic cell perspective. Immunol Rev, in final revision
• Nuanced role for dendritic cell intrinsic IRE1 RNase in the regulation of antitumor adaptive immunity. Frontiers in Immunology, 2023. (PMID: 37346037)
• Efficacy of CD40 agonists is mediated by distinct cDC subsets and subverted by suppressive macrophages. Cancer Research, 2022. (PMID: 35979635)
• The IRE1 inhibitor Kira6 curtails the inflammatory trait of immunogenic anticancer treatments by targeting Hsp60 independent of IRE1. Cell Death Diff  29(1): 230-245 (2021)
• Emerging role of the UPR in tumor immunosurveillance. Trends in Cancer, 2017. (PMID: 28718404)
   

• Lab address: Inflammation Research Center, VIB-University of Ghent, Technologiepark 71, B-9052 Zwijnaarde
• Janssens Lab 
• Inflammation Research Center 
• LinkedIn 
• X (former Twitter): @JanssensLab
• Google Scholar 
• prof. Sophie Janssens is:
  1) involved in EOS LNP-DECODE (EOS network with P. Agostinis (KUL) as spokesperson and Prof. K. Ravichandran as partner at UGent/VIB) to understand how tumor antigens are being decoded by our immune system.
  2) co-organiser of the yearly symposium on Tumor Immunology and Immunotherapy together with An Coosemans (KUL), Jo van Ginderachter (VUB), Evelien Smits (UA) and Abishek Garg (KUL)
• prof. Sophie Janssens provides services to monitor DC maturation state in vivo (human and mouse) by novel designed flow cytometry panels
• prof. Sophie Janssens is interested to receive invitations for presentations or talks