Therapeutic Immunology and Transfusion Medicine – Michael Uhlin’s research group

Our group perform immunological research, mainly focusing on T cells. We work with all T cells but our main focus is unconventional T cells, especially γδ T cells, as these immune cells have not so far been efficiently exploited.

Group portrait

The group is part of the Center for Hematology and Regenerative Medicine (HERM).

About our research

Using state-of-art methods we are looking into γδ T cell reconstitution, and how these cells are affected by different transplant related factors. We also aim to investigate the development and functionality of γδ T cells in detail after hematopoietic stem cell transplantation (HSCT). This could help pave the way for more advanced and targeted approaches in cancer immunotherapy and in infectious diseases, particularly in patients undergoing HSCT.

We also have projects focusing on tumor-infiltrating lymphocytes (TILs) in solid tumors, mainly in ovarian cancer and prostate cancer. We use cancer patient-derived material and isolate lymphocytes from peripheral blood, ascites and tumor which we use for projects involving the characterization and functionality of lymphocytes with emphasis on T-cells. Our aim is to increase the understanding of how the tumor microenvironment can alter the phenotype of TILs and their ability to function and eliminate tumor cells. By using different immunomodulatory approaches, including PD-1 blockade with novel constructs, we try to enhance the responsiveness of TILs ex vivo.

Immunofluorescent staining: Healthy prostates

Acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) are diseases which require treatment with toxic chemotherapy or HSCT. A high burden of leukemic stem cells (LSCs) in AML/MDS patients is associated with high risk of relapse and death, making those cells a good target for new therapies. Bispecific T-cell (BITE) and NK-cell engagers (BIKE) are new classes of immunotherapeutic agents. Their structure and specificity allow them to link a T-/NK-cell to a tumor cell and thereby stimulating effector cell activation, tumor killing and cytokine production. One project within the group is focused on the design and characterization of a BITE and BIKE directed against the molecules expressed LSCs. Our BITE/BIKE would enable the redirection of the T-cell effector function towards malignant cells, directly targeting leukemic cancer cells. The specific depletion of LSCs in AML/MDS patients making the therapy more efficient and less toxic.

Fluorospot immune cells

Publications

Characterization of ascites- and tumor-infiltrating γδ T cells reveals distinct repertoires and a beneficial role in ovarian cancer. Foord E, Arruda LCM, Gaballa A, Klynning C, Uhlin M. Science Translational Medicine. 2021 Jan 20;13(577):eabb0192. doi: 10.1126/scitranslmed.abb0192

DEHT is a suitable plasticizer option for phthalate-free storage of irradiated red blood cells. Larsson L, Ohlsson S, Derving J, Diedrich B, Sandgren P, Larsson S, Uhlin M. Vox Sang. 2021 Jul 15. doi: 10.1111/vox.13177.

Profound Functional Suppression of Tumor-Infiltrating T-Cells in Ovarian Cancer Patients Can Be Reversed Using PD-1-Blocking Antibodies or DARPin® Proteins. Foord E, Klynning C, Schoutrop E, Förster JM, Krieg J, Mörtberg A, Müller MR, Herzog C, Schiegg D, Villemagne D, Fiedler U, Snell D, Kebble B, Mattsson J, Levitsky V, Uhlin M. Journal of Immunololy Research. 2020 Aug 4;2020:7375947. doi: 10.1155/2020/7375947.

Impact of γδ T cells on clinical outcome of hematopoietic stem cell transplantation: systematic review and meta-analysis.Arruda LCM, Gaballa A, Uhlin M. Blood Adv. 2019 Nov 12;3(21):3436-3448. doi: 10.1182/bloodadvances.2019000682.PMID: 31714966

Individualization of Hematopoietic Stem Cell Transplantation Using Alpha/Beta T-Cell Depletion. Rådestad E, Sundin M, Törlén J, Thunberg S, Önfelt B, Ljungman P, Watz E, Mattsson J, Uhlin M. Front Immunol. 2019 Feb 11;10:189. doi: 10.3389/fimmu.2019.00189. eCollection 2019. PMID:30804948

T-cell frequencies of CD8+ γδ and CD27+ γδ cells in the stem cell graft predict the outcome after allogeneic hematopoietic cell transplantation. Gaballa A, Stikvoort A, Önfelt B, Mattsson J, Sundin M, Watz E, Uhlin M. Bone Marrow Transplant. 2019 Oct;54(10):1562-1574. doi: 10.1038/s41409-019-0462-z.PMID:30723262

Graft γδ TCR Sequencing Identifies Public Clonotypes Associated with Hematopoietic Stem Cell Transplantation Efficacy in Acute Myeloid Leukemia Patients and Unravels Cytomegalovirus Impact on Repertoire Distribution. Arruda LCM, Gaballa A, Uhlin M. J Immunol. 2019 Mar 15;202(6):1859-1870. doi: 10.4049/jimmunol.1801448.PMID:30710048

Risk Factors for Severe Acute Graft-versus-Host Disease in Donor Graft Composition. Stikvoort A, Gaballa A, Solders M, Nederlof I, Önfelt B, Sundberg B, Remberger M, Sundin M, Mattsson J, Uhlin M. Biol Blood Marrow Transplant. 2018 Mar;24(3):467-477. doi: 10.1016/j.bbmt.2017.11.026.PMID: 29197674

Funding

  • Barncancerfonden
  • Vetenskapsrådet
  • Cancerfonden
  • Cancerföreningen
  • Radiumhemmet
  • ALF-Stockholm

Staff and contact

Group leader

All members of the group