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Single-cell analysis of immune recognition in chronic myeloid leukemia patients following tyrosine kinase inhibitor discontinuation

Huuhtanen, Jani (författare)
Univ Helsinki, Translat Immunol Res Program, Helsinki, Finland.;Univ Helsinki, Dept Clin Chem & Hematol, Helsinki, Finland.;Helsinki Univ Hosp, Comprehens Canc Ctr, Hematol Res Unit Helsinki, Helsinki, Finland.;Aalto Univ, Dept Comp Sci, Espoo, Finland.;iCAN Digital Precis Canc Med Flagship, Helsinki, Finland.,Helsinki University Central Hospital,University of Helsinki,iCAN Digital Precision Cancer Medicine Flagship,Aalto University
Adnan-Awad, Shady (författare)
Univ Helsinki, Translat Immunol Res Program, Helsinki, Finland.;Univ Helsinki, Dept Clin Chem & Hematol, Helsinki, Finland.;Helsinki Univ Hosp, Comprehens Canc Ctr, Hematol Res Unit Helsinki, Helsinki, Finland.;iCAN Digital Precis Canc Med Flagship, Helsinki, Finland.;Fdn Finnish Canc Inst, Helsinki, Finland.,iCAN Digital Precision Cancer Medicine Flagship,Helsinki University Central Hospital,University of Helsinki
Theodoropoulos, Jason (författare)
Univ Helsinki, Translat Immunol Res Program, Helsinki, Finland.;Univ Helsinki, Dept Clin Chem & Hematol, Helsinki, Finland.;Helsinki Univ Hosp, Comprehens Canc Ctr, Hematol Res Unit Helsinki, Helsinki, Finland.;iCAN Digital Precis Canc Med Flagship, Helsinki, Finland.,University of Helsinki,Helsinki University Central Hospital,iCAN Digital Precision Cancer Medicine Flagship
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Forsten, Sofia (författare)
Univ Helsinki, Translat Immunol Res Program, Helsinki, Finland.;Univ Helsinki, Dept Clin Chem & Hematol, Helsinki, Finland.;Helsinki Univ Hosp, Comprehens Canc Ctr, Hematol Res Unit Helsinki, Helsinki, Finland.;iCAN Digital Precis Canc Med Flagship, Helsinki, Finland.,iCAN Digital Precision Cancer Medicine Flagship,University of Helsinki,Helsinki University Central Hospital
Warfvinge, Rebecca (författare)
Lund University,Lunds universitet,Avdelningen för molekylär hematologi,Institutionen för laboratoriemedicin,Medicinska fakulteten,Stem Cells and Leukemia,Forskargrupper vid Lunds universitet,Division of Molecular Hematology (DMH),Department of Laboratory Medicine,Faculty of Medicine,Lund University Research Groups,Lund Univ, Lund Stem Cell Ctr, Div Mol Hematol, Lund, Sweden.
Dufva, Olli (författare)
Univ Helsinki, Translat Immunol Res Program, Helsinki, Finland.;Univ Helsinki, Dept Clin Chem & Hematol, Helsinki, Finland.;Helsinki Univ Hosp, Comprehens Canc Ctr, Hematol Res Unit Helsinki, Helsinki, Finland.;iCAN Digital Precis Canc Med Flagship, Helsinki, Finland.,Helsinki University Central Hospital,University of Helsinki,iCAN Digital Precision Cancer Medicine Flagship
Bouhlal, Jonas (författare)
Univ Helsinki, Translat Immunol Res Program, Helsinki, Finland.;Univ Helsinki, Dept Clin Chem & Hematol, Helsinki, Finland.;Helsinki Univ Hosp, Comprehens Canc Ctr, Hematol Res Unit Helsinki, Helsinki, Finland.;iCAN Digital Precis Canc Med Flagship, Helsinki, Finland.,University of Helsinki,Helsinki University Central Hospital,iCAN Digital Precision Cancer Medicine Flagship
Dhapola, Parashar (författare)
Lund University,Lunds universitet,Avdelningen för molekylär hematologi,Institutionen för laboratoriemedicin,Medicinska fakulteten,Stem Cells and Leukemia,Forskargrupper vid Lunds universitet,Division of Molecular Hematology (DMH),Department of Laboratory Medicine,Faculty of Medicine,Lund University Research Groups,Lund Univ, Lund Stem Cell Ctr, Div Mol Hematol, Lund, Sweden.
Duan, Hanna (författare)
Univ Helsinki, Translat Immunol Res Program, Helsinki, Finland.;Univ Helsinki, Dept Clin Chem & Hematol, Helsinki, Finland.;Helsinki Univ Hosp, Comprehens Canc Ctr, Hematol Res Unit Helsinki, Helsinki, Finland.;iCAN Digital Precis Canc Med Flagship, Helsinki, Finland.,iCAN Digital Precision Cancer Medicine Flagship,Helsinki University Central Hospital,University of Helsinki
Laajala, Essi (författare)
Univ Helsinki, Translat Immunol Res Program, Helsinki, Finland.;Univ Helsinki, Dept Clin Chem & Hematol, Helsinki, Finland.;Helsinki Univ Hosp, Comprehens Canc Ctr, Hematol Res Unit Helsinki, Helsinki, Finland.;iCAN Digital Precis Canc Med Flagship, Helsinki, Finland.,Helsinki University Central Hospital,University of Helsinki,iCAN Digital Precision Cancer Medicine Flagship
Kasanen, Tiina (författare)
Univ Helsinki, Translat Immunol Res Program, Helsinki, Finland.;Univ Helsinki, Dept Clin Chem & Hematol, Helsinki, Finland.;Helsinki Univ Hosp, Comprehens Canc Ctr, Hematol Res Unit Helsinki, Helsinki, Finland.;iCAN Digital Precis Canc Med Flagship, Helsinki, Finland.,University of Helsinki,Helsinki University Central Hospital,iCAN Digital Precision Cancer Medicine Flagship
Klievink, Jay (författare)
Univ Helsinki, Translat Immunol Res Program, Helsinki, Finland.;Univ Helsinki, Dept Clin Chem & Hematol, Helsinki, Finland.;Helsinki Univ Hosp, Comprehens Canc Ctr, Hematol Res Unit Helsinki, Helsinki, Finland.;iCAN Digital Precis Canc Med Flagship, Helsinki, Finland.,iCAN Digital Precision Cancer Medicine Flagship,University of Helsinki,Helsinki University Central Hospital
Ilander, Mette (författare)
Univ Helsinki, Translat Immunol Res Program, Helsinki, Finland.;Univ Helsinki, Dept Clin Chem & Hematol, Helsinki, Finland.;Helsinki Univ Hosp, Comprehens Canc Ctr, Hematol Res Unit Helsinki, Helsinki, Finland.,Helsinki University Central Hospital,University of Helsinki
Jaatinen, Taina (författare)
Finnish Red Cross Blood Serv, Histocompatibil Testing Lab, Helsinki, Finland. Uppsala Univ, Dept Med Sci, Uppsala, Sweden. Uppsala Univ Hosp, Hematol Sect, Uppsala, Sweden.,Finnish Red Cross Blood Transfusion Service
Olsson-Strömberg, Ulla (författare)
Uppsala universitet,Hematologi,Finnish Red Cross Blood Serv, Histocompatibil Testing Lab, Helsinki, Finland. Uppsala Univ Hosp, Hematol Sect, Uppsala, Sweden.,Uppsala University Hospital
Hjorth-Hansen, Henrik (författare)
St Olavs Hosp, Dept Hematol, Trondheim, Norway.;Norwegian Univ Sci & Technol NTNU, Dept Canc Res & Mol Med, Trondheim, Norway.,Norwegian University of Science and Technology,St. Olav’s University Hospital
Burchert, Andreas (författare)
Philipps Univ Marburg, Dept Hematol Oncol & Immunol, Marburg, Germany.;Univ Med Ctr Giessen & Marburg, Marburg, Germany.,University Hospital Giessen and Marburg
Karlsson, Göran (författare)
Lund University,Lunds universitet,Avdelningen för molekylär hematologi,Institutionen för laboratoriemedicin,Medicinska fakulteten,Stem Cells and Leukemia,Forskargrupper vid Lunds universitet,Division of Molecular Hematology (DMH),Department of Laboratory Medicine,Faculty of Medicine,Lund University Research Groups,Fdn Finnish Canc Inst, Helsinki, Finland.
Kreutzman, Anna (författare)
Univ Helsinki, Translat Immunol Res Program, Helsinki, Finland.;Univ Helsinki, Dept Clin Chem & Hematol, Helsinki, Finland.;Helsinki Univ Hosp, Comprehens Canc Ctr, Hematol Res Unit Helsinki, Helsinki, Finland.,University of Helsinki,Helsinki University Central Hospital
Lähdesmäki, Harri (författare)
Helsinki Univ Hosp, Comprehens Canc Ctr, Hematol Res Unit Helsinki, Helsinki, Finland.,Aalto University
Mustjoki, Satu (författare)
Univ Helsinki, Translat Immunol Res Program, Helsinki, Finland.;Univ Helsinki, Dept Clin Chem & Hematol, Helsinki, Finland.;Helsinki Univ Hosp, Comprehens Canc Ctr, Hematol Res Unit Helsinki, Helsinki, Finland.;iCAN Digital Precis Canc Med Flagship, Helsinki, Finland.,Helsinki University Central Hospital,University of Helsinki,iCAN Digital Precision Cancer Medicine Flagship
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Univ Helsinki, Translat Immunol Res Program, Helsinki, Finland;Univ Helsinki, Dept Clin Chem & Hematol, Helsinki, Finland.;Helsinki Univ Hosp, Comprehens Canc Ctr, Hematol Res Unit Helsinki, Helsinki, Finland.;Aalto Univ, Dept Comp Sci, Espoo, Finland.;iCAN Digital Precis Canc Med Flagship, Helsinki, Finland. Helsinki University Central Hospital (creator_code:org_t)
Springer Nature, 2024
2024
Engelska.
Ingår i: Leukemia. - : Springer Nature. - 0887-6924 .- 1476-5551. ; 38, s. 109-125
Relaterad länk:
https://doi.org/10.1...
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https://uu.diva-port... (primary) (Raw object)
http://dx.doi.org/10... (free)
https://urn.kb.se/re...
https://doi.org/10.1...
https://lup.lub.lu.s...
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  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
Stäng  
  • Immunological control of residual leukemia cells is thought to occur in patients with chronic myeloid leukemia (CML) that maintain treatment-free remission (TFR) following tyrosine kinase inhibitor (TKI) discontinuation. To study this, we analyzed 55 single-cell RNA and T cell receptor (TCR) sequenced samples (scRNA+TCRαβ-seq) from patients with CML (n = 13, N = 25), other cancers (n = 28), and healthy (n = 7). The high number and active phenotype of natural killer (NK) cells in CML separated them from healthy and other cancers. Most NK cells in CML belonged to the active CD56dim cluster with high expression of GZMA/B, PRF1, CCL3/4, and IFNG, with interactions with leukemic cells via inhibitory LGALS9-TIM3 and PVR-TIGIT interactions. Accordingly, upregulation of LGALS9 was observed in CML target cells and TIM3 in NK cells when co-cultured together. Additionally, we created a classifier to identify TCRs targeting leukemia-associated antigen PR1 and quantified anti-PR1 T cells in 90 CML and 786 healthy TCRβ-sequenced samples. Anti-PR1 T cells were more prevalent in CML, enriched in bone marrow samples, and enriched in the mature, cytotoxic CD8+TEMRA cluster, especially in a patient maintaining TFR. Our results highlight the role of NK cells and anti-PR1 T cells in anti-leukemic immune responses in CML.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Hematologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Hematology (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Cancer and Oncology (hsv//eng)

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