Group Fredrik Bergh Thorén
Short description
Research on NK cells and immunotherapy in myeloid leukemia.
Research summary
NK cell biology and cancer immunotherapy
Our research group investigates the biology of natural killer (NK) cells, with a particular focus on how these immune cells recognize and eliminate malignant cells. We aim to understand the molecular mechanisms governing NK cell activation and to translate this knowledge into novel strategies for cancer immunotherapy.
Our research spans from fundamental immunology, molecular and cellular biology, to clinical studies. By combining advanced single-cell technologies, functional genomics, and protein engineering with clinical research, we seek to identify new mechanisms of immune surveillance and explore their therapeutic potential.
Our activities can be divided into four main research areas.
NK cell recognition and tumor immune surveillance
A central research interest in our group is to understand how activating NK cell receptors recognize malignant cells. We have a long-standing interest in the NK cell receptor NKp46, which plays an important role in NK cell-mediated tumor surveillance, although the molecular mechanisms underlying its function remain incompletely understood.
Using genome-wide CRISPR screening, genetic engineering, and functional studies of human NK cells, we investigate the molecular interactions that determine whether malignant cells are recognized and eliminated by NK cells. Our recent work has identified novel mechanisms by which cancer cells evade NK cell cytotoxicity (Kristenson et al., PNAS, 2024).
A major focus of our current research concerns the molecular interplay between NKp46, the death ligand TRAIL, and receptors expressed by malignant cells. We combine experimental and computational approaches to investigate these interactions, their role in NK cell activation, and their potential relevance across different types of cancer.
Development of novel NK cell-based immunotherapies
An important goal of our research is to translate fundamental discoveries in NK cell biology into new therapeutic strategies. Building on our studies of NK cell receptor biology, we are exploring approaches to enhance NK cell recognition and elimination of malignant cells.
Our current projects combine structure-guided protein engineering, computational modeling, and functional screening to develop novel strategies for modulating NK cell activity. We are particularly interested in exploiting natural receptor-ligand interactions for the development of engineered immune cells, including chimeric antigen receptor (CAR)-NK cells.
These efforts are part of our expanding activities in advanced therapy medicinal products (ATMPs) and our long-term ambition is to translate discoveries in NK cell biology into innovative cancer treatments.
Hematopoiesis and myeloid malignancies
Our group has a long-standing interest in myeloid malignancies, particularly acute and chronic myeloid leukemia (AML and CML). Using single-cell RNA sequencing and CITE-seq, we investigate normal and malignant hematopoiesis, with a particular focus on hematopoietic stem and progenitor cells.
Recent studies have provided new insights into human hematopoietic differentiation and the cellular heterogeneity of leukemic stem cells (Komic et al., Nature Communications, 2025; Haematologica, 2025; Nilsson et al., bioRxiv, 2023).
In parallel, we investigate the role of NK cells in immunotherapy of myeloid malignancies. Our previous work has demonstrated associations between NK cell immunogenetics, NK cell repertoire composition, and clinical outcome following relapse-preventive immunotherapy with histamine and IL-2 in AML (Hallner et al., Blood, 2019; Hussein et al., Journal for ImmunoTherapy of Cancer, 2023).
NK cell-neutrophil interactions and inflammation
Another research area in our group focuses on the interplay between natural killer cells and neutrophils during inflammation. In collaboration with other research groups, we investigate how these innate immune cells communicate and contribute to the regulation of inflammatory responses.
Using advanced single-cell technologies, including scRNA-seq and CITE-seq, we aim to characterize neutrophil heterogeneity in peripheral blood and inflammatory tissues, and to identify functionally distinct neutrophil populations.
We also investigate how neutrophils influence cytokine activity and NK cell responses in inflammatory environments. These studies aim to uncover novel mechanisms of immune regulation and may provide insights relevant to the development of future immunomodulatory therapies.
Current group members
Fredrik Bergh Thorén, group leader, Orcid
Erna Islamagic, PhD, Postdoc
Johan Gustafsson, PhD, Postdoc
Linnea Blomén, PhD, Postdoc
Chiara Badami, PhD, Postdoc
Anne Wöhr, PhD student
Ebba Danielsson, PhD student
William Lager, PhD student
Thomas Gustafsson, Amanuens
Selected publications
- Deletion of the TMEM30A gene enables leukemic cell evasion of NK cell cytotoxicity.
Kristenson L, Badami C, Ljungberg A, Islamagic E, Tian Y, Xie G, Hussein BA, Pesce S, Tang KW, Thorén FB. Proc Natl Acad Sci U S A. 2024 Apr 9;121(15):e2316447121. doi: 10.1073/pnas.2316447121. Epub 2024 Apr 1.PMID: 38557174
- NKG2A gene variant predicts outcome of immunotherapy in AML and modulates the repertoire and function of NK cells.
Hussein BA, Kristenson L, Pesce S, Wöhr A, Tian Y, Hallner A, Brune M, Hellstrand K, Tang KW, Bernson E, Thorén FB. J Immunother Cancer. 2023 Aug;11(8):e007202. doi: 10.1136/jitc-2023-007202.PMID: 37648262
- The HLA-B -21 dimorphism impacts on NK cell education and clinical outcome of immunotherapy in acute myeloid leukemia.
Hallner A, Bernson E, Hussein BA, Ewald Sander F, Brune M, Aurelius J, Martner A, Hellstrand K, Thoren FB. Blood 2019, 133:1479-1488S
- Cytomegalovirus Serostatus Affects Autoreactive NK Cells and Outcomes of IL2-Based Immunotherapy in Acute Myeloid Leukemia.
Bernson E, Hallner A, Sander FE, Nicklasson M, Nilsson MS, Christenson K, Aydin E, Liljeqvist JA, Brune M, Foa R, Aurelius J, Martner A, Hellstrand K, Thoren FB. Cancer Immunol Res 2018, 6:1110-1119.
- Impact of killer-immunoglobulin-like receptor and human leukocyte antigen genotypes on the efficacy of immunotherapy in acute myeloid leukemia.
Bernson E, Hallner A, Sander FE, Wilsson O, Werlenius O, Rydström A, Kiffin R, Brune M, Foà R, Aurelius J, Martner A, Hellstrand K, Thorén FB. Leukemia. 2017 Dec;31(12):2552-2559. doi: 10.1038/leu.2017.151.