Research group Susanne Gabrielsson

Extracellular vesicles (EV) are nanosized cell-to-cell messengers released from all cells. They can induce immune stimulation or inhibition depending on their cell origin. EVs have been tested in humans as cancer immunotherapy, and we want to optimize them for cancer immunotherapy. We also work to characterize EVs in patients with cancer and lung diseases, both to understand their function to target them in therapeutic approaches, and to develop them as biomarkers for disease.

Extracellular vesicles in cancer and lung diseases

We work to understand how extracellular vesicles (EVs), especially exosomes, influence the immune system. They work as messengers between cells and can deliver cargo such as enzymes, mRNA, microRNA and immunoregulatory proteins. During the last years, results from us and others have revealed that EVs exist in most body fluids. We have made the discovery of EVs in bronchoalveolar lavage (BAL) fluid and also in breast milk. We have reported that BAL EVs from patients with both asthma and sarcoidosis are pro-inflammatory and might contribute to pathogenesis of lung diseases. In contrast, milk EVs inhibit cytokine production, suggesting that milk EVs might protect the child from allergies.

Extracellular vesicles consists of exosomes, which are released from the endosomal compartment, and microvesicles, which bud from the cell surface. Illustrator: Casper Wahlund.

The mechanism of action of EVs in vivo is not fully understood, but they seem to have functions similar to those of whole cells. EVs from antigen presenting cells contain both MHC I and II, as well as co-stimulatory molecules, and can stimulate T cells in vitro. This led to the idea that EVs generated in vitro might be used for cancer therapy. Indeed, dendritic cell derived EVs constitute novel therapeutic vehicles, but still mechanisms for activation are unclear and should be optimized. We have shown that EVs function as a Th1-inducing adjuvant through a B cell dependent mechanism and that the effect of an NKT cell ligand is synergized when bound to EVs, leading to tumor destruction. This raises the hopes that EVs could be used as cancer treatment in the future.

Major Aims

  1. To elucidate the molecular mechanisms behind EV induced immune stimulation.
  2. To understand the role of EVs in inflammatory diseases such as Asthma, COPD and Sarcoidosis.
  3. To potentiate immunogenicity of EVs by exosome engineering.

Significance

We hope to find more efficient exosome-based therapies for cancer, autoimmunity and allergy. This work might also lead to improved methods to detect cancer and lung diseases.

Group members

Susanne Gabrielsson

Professor, Research group leader.
Gabrielsson S
K2 Department of Medicine, Solna
Group picture - Photo: Annika Jouper

Research support

  • Swedish Research Council.
  • The Swedish Cancer Foundation.
  • The Swedish Heart and Lung Foundation.
  • Cancer and Allergy Foundation.
  • The Karolinska Institute.
  • The Radiumhemmets Research Foundations.

Publications

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