Scholarlink

<p>Natural killer (NK) cells play a crucial role in immune surveillance by recognizing and eliminating tumor cells. However, tumors employ various mechanisms to evade NK cell-mediated immunity. NKp30 is a potent activating receptor on NK cells, but its function can be inhibited by specific ligands secreted by cancer cells. Here, we identified dipeptidase 1 (DPEP1) as a novel ligand for NKp30 in KM12C colon cancer cells, using co-immunoprecipitation, confocal microscopy, and flow cytometry. We examined how the DPEP1–NKp30 interaction affects NK cell activity and found that NK cytotoxicity increased in KM12C cells with DPEP1 knockdown but was significantly reduced in HCT116 cells overexpressing DPEP1. We further demonstrated that DPEP1 is secreted via extracellular vesicles and that its interaction with NKp30 suppressed the expression and secretion of perforin 1, granzyme B, CD107a, and interferon-γ in NK92 cells. In a xenograft mouse model treated with NK92 cells, tumors derived from HCT116/DPEP1 cells were significantly larger than those from HCT116/mock cells. Using peripheral blood-derived human NK cells, we confirmed that DPEP1 inhibited both cytotoxicity and granzyme B secretion. These findings suggest that disrupting the DPEP1–NKp30 interaction may enhance NK cell-mediated cytotoxicity and represent a novel therapeutic strategy for cancer immunotherapy.</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

Attenuation of natural killer cell cytotoxicity by interaction between NKp30 of NK cells and dipeptidase 1 of colon cancer cells

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年10月6日

查看全文
  • Jong-Tae Kim,
  • Eun Sun Park,
  • Yo Sep Hwang,
  • Hyang Ran Yoon,
  • Suk Ran Yoon,
  • Hee Jun Cho,
  • Hee Gu Lee

摘要

Natural killer (NK) cells play a crucial role in immune surveillance by recognizing and eliminating tumor cells. However, tumors employ various mechanisms to evade NK cell-mediated immunity. NKp30 is a potent activating receptor on NK cells, but its function can be inhibited by specific ligands secreted by cancer cells. Here, we identified dipeptidase 1 (DPEP1) as a novel ligand for NKp30 in KM12C colon cancer cells, using co-immunoprecipitation, confocal microscopy, and flow cytometry. We examined how the DPEP1–NKp30 interaction affects NK cell activity and found that NK cytotoxicity increased in KM12C cells with DPEP1 knockdown but was significantly reduced in HCT116 cells overexpressing DPEP1. We further demonstrated that DPEP1 is secreted via extracellular vesicles and that its interaction with NKp30 suppressed the expression and secretion of perforin 1, granzyme B, CD107a, and interferon-γ in NK92 cells. In a xenograft mouse model treated with NK92 cells, tumors derived from HCT116/DPEP1 cells were significantly larger than those from HCT116/mock cells. Using peripheral blood-derived human NK cells, we confirmed that DPEP1 inhibited both cytotoxicity and granzyme B secretion. These findings suggest that disrupting the DPEP1–NKp30 interaction may enhance NK cell-mediated cytotoxicity and represent a novel therapeutic strategy for cancer immunotherapy.