Scholarlink

<p>Natural Killer (NK) cells naturally recognize and eliminate leukemic cells. However, the molecular interactions that govern these responses are diverse due to the large number of activating and inhibitory NK receptors that modulate NK functions and the diversity of corresponding ligands that are differentially expressed in acute lymphoblastic and myeloblastic leukemias. We identified resting NKG2A<sup>+</sup> NK cells and NKG2A<sup>+</sup>KIR<sup>+</sup> NK cell subsets as the most effective in eliminating lymphoid and myeloid leukemic cells respectively. The NKG2A<sup>+</sup>KIR<sup>±</sup>CD57<sup>−</sup> cell subsets show high expression of activating receptors and a functional transcriptomic profile, but differ in KIR2DL5 expression. The frequency of KIR2DL5<sup>+</sup> NK cells increases with the number of expressed KIR. Furthermore, KIR2DL5 is preferentially co-expressed with KIR2DL1 and is negatively regulated by NKG2A. Of note, CD57 expression, regardless of the NK cell subset considered, is associated with reduced receptor expression, consistent with its reduced cytotoxic potential. Furthermore, molecular interactions between NK cells and leukemic cells influence NK cell responses, particularly the inhibitory KIR2DL5-PVR axis. The integration of these data is of importance for the optimization of NK cell-based immunotherapies, as the selection of NK cell donors represents a key parameter for the improvement of these therapies.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Molecular Interactions Between NK Cells and Acute Leukemic Cells: KIR2DL5 Drastically Limits NK Cell Responses

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年7月29日

查看全文
  • Enora Ferron,
  • Maxime Jullien,
  • Martin Braud,
  • Gaëlle David,
  • Cynthia Fourgeux,
  • Mathilde Bastien,
  • Perla Salameh,
  • Catherine Willem,
  • Nolwenn Legrand,
  • Alexandre Walencik,
  • Thierry Guillaume,
  • Pierre Peterlin,
  • Alice Garnier,
  • Amandine Lebourgeois,
  • Katia Gagne,
  • Jeremie Poschmann,
  • Patrice Chevallier,
  • Christelle Retière

摘要

Natural Killer (NK) cells naturally recognize and eliminate leukemic cells. However, the molecular interactions that govern these responses are diverse due to the large number of activating and inhibitory NK receptors that modulate NK functions and the diversity of corresponding ligands that are differentially expressed in acute lymphoblastic and myeloblastic leukemias. We identified resting NKG2A+ NK cells and NKG2A+KIR+ NK cell subsets as the most effective in eliminating lymphoid and myeloid leukemic cells respectively. The NKG2A+KIR±CD57− cell subsets show high expression of activating receptors and a functional transcriptomic profile, but differ in KIR2DL5 expression. The frequency of KIR2DL5+ NK cells increases with the number of expressed KIR. Furthermore, KIR2DL5 is preferentially co-expressed with KIR2DL1 and is negatively regulated by NKG2A. Of note, CD57 expression, regardless of the NK cell subset considered, is associated with reduced receptor expression, consistent with its reduced cytotoxic potential. Furthermore, molecular interactions between NK cells and leukemic cells influence NK cell responses, particularly the inhibitory KIR2DL5-PVR axis. The integration of these data is of importance for the optimization of NK cell-based immunotherapies, as the selection of NK cell donors represents a key parameter for the improvement of these therapies.