The sarcoma tumor microenvironment (TME) team focuses on understanding how malignant and non-malignant cells are affected and educated by each other during sarcoma progression in children and adults
I am Team leader for the Sarcoma Tumor Microenvironment Team at BioClinicum. Our main interest is to characterize how tumor cells make use of, and reprogram, normal host cells to participate in sarcoma progression. Cellular crosstalk between different cell types is essential both during tumor initiation and metastasis. In summary, we hope to identify novel biomarkers and therapeutic approaches with principally different modes of action compared to the aggressive multimodal treatments of today.
During my PhD studies in the Prof Ulf Eriksson lab at the Ludwig Institute for Cancer Research Ltd, I became interested in platelet-derived growth factor (PDGF) signaling. My thesis work focused on characterizing how two of the most recently discovered PDGF ligands were activated by proteolytic activation.
I continued to explore the prognostic and functional role of PDGF ligands and receptors in pediatric rhabdomyosarcoma during my postdoc work in the Prof Arne Östman lab at the Cancer Center Karolinska.
Cells of the tumor microenvironment control tumor growth, metastasis and response to treatment. These aspects of tumor biology are well studied in tumors derived from epithelial cells, but much less described in sarcomas. These malignant tumors of mesenchymal origin can be found almost anywhere in the body and include subtypes like rhabdomyosarcoma, undifferentiated pleomorphic sarcoma, and liposarcoma.
We have currently developed several distinct in vitro and in vivo model systems for sarcoma TME studies. Methods used in the lab, or together with our national or international collaborators, include immunostaining (multiplexing) of human or mouse tissue material, microscopy/image analysis, advanced cell culture, qPCR and gene expression analysis/bioinformatics, and flow cytometry. Our projects are translational and involve collaborations with bioinformaticians, pathologists, oncologists and surgeons.
Ongoing projects focus on immune cell characterization, tertiary lymphoid structures, and digital image analysis. We also study cellular crosstalk with mesenchymal stromal cells in cell culture and in zebrafish. Molecular factors of interest include PDGF, CTGF, and IGF/IGFBP5.
If you are interested and would like to help out in our research, please send an email to email@example.com. We can also assist in upcoming calls/project applications for postdocs or other visiting scientists. Publications originating from our research are listed below:
1. Tsagkozis P, Gonzalez Molina J, Georgoudaki A, Lehti K, Carlson J, Lundqvist A, Haglund F, Ehnman M. Sarcoma tumor microenvironment. In: Birbrair A. (ed.) Tumor Microenvironment – Novel Concepts. Springer. In press.
2. Su Y, Tsagkozis P, Papakonstantinou A, Tobin NP, Gultekin O, Malmerfelt A, Ingelshed K, Neo SY, Lundquist J, Chaabane W, Nisancioglu MH, Leiss LW, Östman A, Bergh J, Sedimbi S, Lehti K, Lundqvist A, Stragliotto CL, Haglund F, and Ehnman M. CD11c-CD8 spatial cross presentation: A novel approach to link immune surveillance and patient survival in soft tissue sarcoma. Cancers 2021;Mar 9;13(5):1175. doi: 10.3390/cancers13051175.
3. Ehnman M, Chaabane W, Haglund F, Tsagkozis P. The Tumor Microenvironment of Pediatric Sarcoma: Mesenchymal Mechanisms Regulating Cell Migration and Metastasis. Curr Oncol Rep 2019; 21(10):90. doi:10.1007/s11912-019-0839-6.
4. Tsagozis P, Augsten M, Zhang Y, Li T, Haglund F, Bergh J, Hesla A, Tobin NP, Ehnman M. An immunosuppressive macrophage profile attenuates the prognostic impact of CD20 positive B cells in human soft-tissue sarcoma. Cancer Immunol Immunother 2019;68(6):927-936. doi:10.1007/s00262-019-02322-y
5. Moreno-Ruiz P, Wik Leiss L, Mezheyeuski A, Ehnman M. Double Immunohistochemistry and Digital Image Analysis. Methods Mol Biol 2019;1913:3-11. doi:10.1007/978-1-4939-8979-9_1
6. Lin Y, Seger N, Tsagkozis P, Hesla AC, Ghaderi M, Chen Y, Ehnman M, Warsito D, Wejde J, Larsson O, Haglund F. Telomerase promoter mutations and copy number alterations in solitary fibrous tumours. J Clin Pathol 2018;71(9):832-839. doi:10.1136/jclinpath-2018-205132
7. Gladh H, Folestad EB, Muhl L, Ehnman M, Tannenberg P, Lawrence AL, et al. Mice Lacking Platelet-Derived Growth Factor D Display a Mild Vascular Phenotype. PLoS One. 2016;11(3):e0152276.
8. Ehnman M, Larsson O. Microenvironmental Targets in Sarcoma. Front Oncol. 2015;5:248.
9. Paulsson J, Ehnman M, Ostman A. PDGF receptors in tumor biology: prognostic and predictive potential. Future Oncol. 2014;10(9):1695-708.
10. Ehnman M, Ostman A. Therapeutic targeting of platelet-derived growth factor receptors in solid tumors. Expert Opin Investig Drugs. 2014;23(2):211-26.
11. Ehnman M, Missiaglia E, Folestad E, Selfe J, Strell C, Thway K, et al. Distinct effects of ligand-induced PDGFRalpha and PDGFRbeta signaling in the human rhabdomyosarcoma tumor cell and stroma cell compartments. Cancer Res. 2013;73(7):2139-49.
12. Ehnman M, Li H, Fredriksson L, Pietras K, Eriksson U. The uPA/uPAR system regulates the bioavailability of PDGF-DD: implications for tumour growth. Oncogene. 2009;28(4):534-44.
13. Fredriksson L, Ehnman M, Fieber C, Eriksson U. Structural requirements for activation of latent platelet-derived growth factor CC by tissue plasminogen activator. J Biol Chem. 2005;280(29):26856-62.
14. Cronwright G, Le Blanc K, Gotherstrom C, Darcy P, Ehnman M, Brodin B. Cancer/testis antigen expression in human mesenchymal stem cells: down-regulation of SSX impairs cell migration and matrix metalloproteinase 2 expression. Cancer Res. 2005;65(6):2207-15.
Ostman A, Ehnman M. Läkemedel i tidig utveckling –lovande fynd utanför immunonkologins huvudfåra (2019) Onkologi i Sverige nr 6-19.
In collaboration with OTW/The Childhood Cancer Fund: Barncancerrapporten 2018, Barn&Cancer 2017 (mjukdelssarkom), Barncancerrapporten 2015
PhD student course, Tumor microenvironment, Dept. of Oncology-Pathology, KI (2017-present), Main course organizer and contact 2020, 2021
Biomedicine programme, course Molecular Medicine-Oncology, Dept. of Oncology-Pathology, KI (2019-present)
Biomedicine master programme, course Frontiers in Biomedicine, Dept of MTC, KI (2021)
Biomedicine programme, course Molecular Oncology and Biostatistics, Dept. of Oncology-Pathology, KI (2018)
Medical School, Human genetic disease and cell biology, Dept. of Cell- and Molecular Biology, KI (2004-2010)
PhD in Medical Science/Cell- and Molecular Biology, Karolinska Institutet/Ludwig Institute for Cancer Research Ltd, Stockholm Branch
Thesis title: “Activation of the Novel PDGFs by Plasminogen Activators in Tumorigenesis” http://diss.kib.ki.se/2010/978-91-7409-898-3/, date of defence: May 21, 2010
Academic honours, awards and prizes
Assistant Professorship, 4 years award, The Swedish Childhood Cancer Fund, 2019
Post doctoral fellowship 2+2 years award, The Swedish Childhood Cancer Fund, 2011
Top 10 finalist and invited speaker, Oncology Abstract Competition, MedImmune, Cambridge, United Kingdom (2011)
Pitmans Examination Institute Certificate in English, Advanced level, Embassy CES, Oxford (2003)
The sarcoma tumor microenvironment team is grateful for generous past and present funding from Barncancerfonden, Cancerföreningen, Åke Wibergs stiftelse, Mary Béves stiftelse för barncancerforskning, Alex och Eva Wallströms stiftelse and Tornspiran