بيانات النشر: Uppsala universitet, Hematologi
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.
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.
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.
Lund Univ, Lund Stem Cell Ctr, Div Mol Hematol, Lund, Sweden.
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.
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 Serv, Histocompatibil Testing Lab, Helsinki, Finland. Uppsala Univ Hosp, Hematol Sect, Uppsala, Sweden.
St Olavs Hosp, Dept Hematol, Trondheim, Norway.;Norwegian Univ Sci & Technol NTNU, Dept Canc Res & Mol Med, Trondheim, Norway.
Philipps Univ Marburg, Dept Hematol Oncol & Immunol, Marburg, Germany.;Univ Med Ctr Giessen & Marburg, Marburg, Germany.
Fdn Finnish Canc Inst, Helsinki, Finland.
Helsinki Univ Hosp, Comprehens Canc Ctr, Hematol Res Unit Helsinki, Helsinki, Finland.
نبذة مختصرة : 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.
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