Research group Susanne Gabrielsson
Extracellular vesicles in immunity
Our central theme is to understand the immunological effects of extracellular vesicles (EVs). EVs are natural nanovesicles released from all cells and are present in all body fluids. We work both with clinical studies and in different disease models. Our work has revealed that EVs are major players in lung diseases such as asthma and sarcoidosis. We are also studying the immune response to dendritic cell derived EVs, in order to develop EV based immunotherapies for cancer.
Projects
Understanding the role of EVs in lung diseases
EVs are packed with information such as RNA, proteins and lipids. Since our discovery of EVs in bronchoalveolar lavage fluid in 2003, we have demonstrated that EVs can have pro-inflammatory functions in lung diseases. Now we investigate the molecular basis for this, in order to develop new treatments for asthma, sarcoidosis and Chronic Obstructive Lung Disease (COPD).
EVs as a driver for cancer progression
Cancer cells that mutate to produce EVs that inhibit immune responses, promote blood vessel formation or cell migration have an advantage over other cells. We are analyzing EVs from cancer patients to find new therapeutic targets in cancer.
EVs as biomarkers for disease
EVs are ideal as biomarkers for disease, as they are released from all cells and represent a snapshot of the state of the originating cell, they can therefore represent a liquid biopsy. We develop new methods for EV detection and we analyze patient samples in order to develop biomarkers for early detection, disease monitoring or treatment guidance in both lung diseases and cancer.
EVs as cancer immunotherapy
Currently we are working on different ways to boost immunogenicity of EVs. In different model systems, we engineer EVs to induce cancer-specific immune responses, thereby developing new EV-based cancer treatments, with more specificity and less side effects than current treatments.
EVs in breast milk
Breast milk contains a lot of immune information delivered to the newborn baby. We have discovered that milk contains EVs, and now we are both trying to understand their immunological role, and work to use them in therapeutic applications in e.g. allergies.
Susanne Gabrielsson
Professor, Research group leader.The research group
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Annemarijn Offens
Clinical assistantAnnemarijn has a bachelor’s degree in medicine (University of Groningen, the Netherlands) and a master’s degree in Biomedical Sciences (Radboud University, the Netherlands). In September 2019, she started as a doctoral student in Susanne Gabrielson’s group, to study the modulation of adaptive immune responses using antigen-loaded extracellular vesicles.
Loïc did his master’s studies Life Sciences and Technology at EPFL in Lausanne, Switzerland, and started working on extracellular vesicles during his master thesis carried out at Weill Cornell Medicine in the research group of Prof. David Lyden. He started his PhD in 2019 focusing on the characterization of extracellular vesicles from several diseases to better understand their function and use them as novel therapeutic tools.
Loes did her master´s studies Molecular and Cellular Life Sciences at University Utrecht, Netherlands. She started working with vesicles derived from boar spermatozoa using electron microscopy during her major master´s internship in Veterinary Medicine at Utrecht University. Following this path, she started her minor masters´ internship working on the comparison of different isolation methods of extracellular vesicles at Karolinska Institutet in the group of Susanne Gabrielsson. In 2020, she started her PhD focusing on optimizing bone-marrow dendritic cell-derived extracellular vesicles (BMDC EVs) for cancer immunotherapy using mouse models.
Previous Lab members
Former Post Docs
Former PhD Students
Former Co-supervised PhD Students
Selected publications
Cancer vaccine papers:
Veerman RE, Gucluler Akpinar G, Offens A, Steiner L, Larssen P, Lundqvist A, Karlsson MCI, Gabrielsson S. Antigen-Loaded Extracellular Vesicles Induce Responsiveness to Anti-PD-1 and Anti-PD-L1 Treatment in a Checkpoint Refractory Melanoma Model.Veerman RE, Akpinar GG, Offens A, Steiner L, Larssen P, Lundqvist A, Karlsson MCI, Gabrielsson S
Cancer Immunol Res 2023 Feb;11(2):217-227 Cancer Immunol Res. 2022 Dec 22:CIR-22-0540. doi: 10.1158/2326-6066.CIR-22-0540. Epub ahead of print. PMID: 36546872.
Larssen P, Veerman RE, Akpinar GG, Hiltbrunner S, Karlsson MCI, Gabrielsson S. Allogenicity Boosts Extracellular Vesicle-Induced Antigen-Specific Immunity and Mediates Tumor Protection and Long-Term Memory In Vivo. J Immunol. 2019 Aug 15;203(4):825-834. doi: 10.4049/jimmunol.1801628. Epub 2019 Jul 10. PubMed PMID: 31292216.
Hiltbrunner S, Larssen P, Eldh M, Martinez-Bravo MJ, Wagner AK, Karlsson MC, Gabrielsson S. Exosomal cancer immunotherapy is independent of MHC molecules on exosomes. Oncotarget. 2016 Jun 21;7(25):38707-38717. doi: 10.18632/oncotarget.9585. PubMed PMID: 27231849; PubMed Central PMCID: PMC5122422.
Gehrmann U, Hiltbrunner S, Georgoudaki AM, Karlsson MC, Näslund TI, Gabrielsson S. Synergistic induction of adaptive antitumor immunity by codelivery of antigen with α-galactosylceramide on exosomes. Cancer Res. 2013 Jul 1;73(13):3865-76. doi: 10.1158/0008-5472.CAN-12-3918. Epub 2013 May 8. PubMed PMID: 23658368.
Näslund TI, Gehrmann U, Qazi KR, Karlsson MC, Gabrielsson S. Dendritic cell-derived exosomes need to activate both T and B cells to induce antitumor immunity. J Immunol. 2013 Mar 15;190(6):2712-9. doi: 10.4049/jimmunol.1203082. Epub 2013 Feb 15. PubMed PMID: 23418627.
Bladder cancer papers:
Proteomic profiling of tissue exosomes indicates continuous release of malignant exosomes in urinary bladder cancer patients, even with pathologically undetectable tumour Maria Eldh, Michael Mints, Stefanie Hiltbrunner, Sam Ladjevardi, Farhood Alamdari, Markus Johansson, Tomasz Jakubczyk, Rosanne E Veerman, Ola Winqvist, Amir Sherif, Susanne Gabrielsson. Cancers 13 (13), 3242
Urinary exosomes from bladder cancer patients show a residual cancer phenotype despite complete pathological downstaging Stefanie Hiltbrunner, Michael Mints, Maria Eldh, Robert Rosenblatt, Benny Holmström, Farhood Alamdari, Markus Johansson, Rosanne E Veerman, Ola Winqvist, Amir Sherif, Susanne Gabrielsson. Scientific reports 10 (1), 1-9
Exosomes in urine retain a malignant protein profile after primary tumour ablation in patients with invasive urinary bladder cancer Michael Mints, Stefanie Hiltbrunner, Maria Eldh, Robert Rosenblatt, Benny Holmström, Farhood Alamdari, Markus Johansson, Johan Hansson, Jonas Vasko, Ola Winqvist, Amir Sherif, Susanne Gabrielsson. Scandinavian journal of urology 51, 38-39
Lung papers:
Sarcoidosis exosomes stimulate monocytes to produce pro-inflammatory cytokines and CCL2
Casper JE Wahlund, Gozde Gucluler Akpinar, Loïc Steiner, Ahmed Ibrahim, Elga Bandeira, Rico Lepzien, Ana Lukic, Anna Smed-Sörensen, Susanna Kullberg, Anders Eklund, Johan Grunewald, Susanne Gabrielsson. Scientific reports 10 (1), 1-11
Exosomes and cells from lung cancer pleural exudates transform LTC4 to LTD4, promoting cell migration and survival via CysLT1 Ana Lukic, Casper JE Wahlund, Cristina Gómez, Daniel Brodin, Bengt Samuelsson, Craig E Wheelock, Susanne Gabrielsson, Olof Rådmark. Cancer Letters 444, 1-8
The impact of extracellular vesicles on inflammatory processes in pulmonary sarcoidosis C Wahlund, G Gucluler, R Lepzien, A Smed-Sorenssen, S Gabrielsson. SCANDINAVIAN JOURNAL OF IMMUNOLOGY 86 (4), 254-254
Pulmonary sarcoidosis is associated with exosomal vitamin D–binding protein and inflammatory molecules Maria-Jose Martinez-Bravo, Casper JE Wahlund, Khaleda Rahman Qazi, Robert Moulder, Ana Lukic, Olof Rådmark, Riitta Lahesmaa, Johan Grunewald, Anders Eklund, Susanne Gabrielsson. Journal of Allergy and Clinical Immunology 139 (4), 1186-1194
Pulmonary epithelial cancer cells and their exosomes metabolize myeloid cell-derived leukotriene C4 to leukotriene D4 Ana Lukic, Jie Ji, Helena Idborg, Bengt Samuelsson, Lena Palmberg, Susanne Gabrielsson, Olof Rådmark. Journal of lipid research 57 (9), 1659-1669
Other:
Veerman RE, Teeuwen L, Czarnewski P, Güclüler Akpinar G, Sandberg A, Cao X, Pernemalm M, Orre LM, Gabrielsson S, Eldh M. Molecular evaluation of five different isolation methods for extracellular vesicles reveals different clinical applicability and subcellular origin. J Extracell Vesicles. 2021 Jul;10(9):e12128. doi: 10.1002/jev2.12128. Epub 2021 Jul 22. PubMed PMID: 34322205; PubMed Central PMCID: PMC8298890.