Scholarlink

<p>Cutaneous T-Cell Lymphoma (CTCL) is a non-Hodgkin’s lymphoma involving malignant skin-homing T-cells, characterized by variable severity and limited treatment options. Our study shows that patient samples and derived cell lines express CD38 on CTCL cells, and αCD38 antibodies effectively target CD38 in a mouse model. In vivo αCD38 antibody treatment led to the loss of CD38 expression in residual tumor cells, highlighting the need for innovative strategies to improve CTCL outcomes despite the CD38 loss in residual tumor cells. To investigate the role of CD38 in CTCL pathology, we used CRISPR-Cas9 to create CD38-deficient (CD38<sup>KO</sup>) CTCL cells. These CD38<sup>KO</sup> cells showed higher expression of oncogenes <i>B-catenin</i>, <i>TCF7</i>, and <i>BCL6</i>, along with reduced migration. Elevated NAD+ levels in CD38<sup>KO</sup> cells increased cellular respiration after CD38 inhibition in CD38<sup>WT</sup> cells. In vivo, CD38<sup>KO</sup> cell transplants led to more aggressive tumors, likely due to elevated β-catenin, Bcl6, and Tcf-1 signaling. Prior research in multiple myeloma showed αCD38 antibody efficacy relies on CD38 expression. We discovered that panobinostat, a histone deacetylase inhibitor, increased surface CD38 expression in CTCL cells dose-dependently. Combining panobinostat with αCD38 antibody in a CTCL mouse model significantly improved survival compared to the antibody alone, underscoring CD38’s therapeutic potential in CTCL.</p><p></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

CD38 in the pathobiology of cutaneous T-cell lymphoma and the potential for combination therapeutic intervention

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年3月8日

查看全文
  • Colleen Isabelle,
  • Amy Boles,
  • Kathleen McConnell,
  • Robyn Keller,
  • Rachel Burzinski,
  • Zachary Hutchins,
  • Giulia Calabretto,
  • Lara Cheslow,
  • Jonathan Xu,
  • Nitin Chakravarti,
  • Pierluigi Porcu,
  • Neda Nikbakht,
  • Anjali Mishra

摘要

Cutaneous T-Cell Lymphoma (CTCL) is a non-Hodgkin’s lymphoma involving malignant skin-homing T-cells, characterized by variable severity and limited treatment options. Our study shows that patient samples and derived cell lines express CD38 on CTCL cells, and αCD38 antibodies effectively target CD38 in a mouse model. In vivo αCD38 antibody treatment led to the loss of CD38 expression in residual tumor cells, highlighting the need for innovative strategies to improve CTCL outcomes despite the CD38 loss in residual tumor cells. To investigate the role of CD38 in CTCL pathology, we used CRISPR-Cas9 to create CD38-deficient (CD38KO) CTCL cells. These CD38KO cells showed higher expression of oncogenes B-catenin, TCF7, and BCL6, along with reduced migration. Elevated NAD+ levels in CD38KO cells increased cellular respiration after CD38 inhibition in CD38WT cells. In vivo, CD38KO cell transplants led to more aggressive tumors, likely due to elevated β-catenin, Bcl6, and Tcf-1 signaling. Prior research in multiple myeloma showed αCD38 antibody efficacy relies on CD38 expression. We discovered that panobinostat, a histone deacetylase inhibitor, increased surface CD38 expression in CTCL cells dose-dependently. Combining panobinostat with αCD38 antibody in a CTCL mouse model significantly improved survival compared to the antibody alone, underscoring CD38’s therapeutic potential in CTCL.