Scholarlink

<p>Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive tumor characterized by its ability to create an immunosuppressive tumor microenvironment. Here, using robust 3D co-culture systems, samples from PDAC patients and murine in vivo models, we described a novel immune evasion mechanism used by PDAC to inhibit the anti-tumor activity of B lymphocytes: We provide evidence that pancreatic cancer suppresses the B cell-specific transcriptional program while enforcing their reprogramming into functional macrophages. Thus, we hypothesize that B cells undergo transdifferentiation under the influence of PDAC, by losing their lymphoid identity and acquiring a myeloid immunosuppressive phenotype. This drastic change is enacted by the loss of <i>Pax5</i> expression. Importantly, our results showed that the Ex-B cells efficiently become phagocytic and produce soluble proteins that are known to enhance cancer cell survival and proliferation. This suggests that the PDAC-induced B cell to macrophage transdifferentiation pathway is functionally relevant and hence could serve as an immunotherapeutic target.</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

Pancreatic cancer induces B cell lineage plasticity via Pax5 inhibition to sustain immunosuppression

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年6月2日

查看全文
  • Ali Kassem,
  • Nataly Naser Al Deen,
  • Sun Yifeng,
  • Chau Fang,
  • Laura Mayer,
  • Lingling Zhang,
  • Paul Kunath,
  • Thomas Wirth,
  • Uwe Knippschild,
  • Mohammad Rahbari,
  • Mathias Heikenwälder,
  • Bo Kong,
  • Cornelia Brunner,
  • Alexander N. R. Weber,
  • Nuh Rahbari,
  • Hend Abdelrasoul

摘要

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive tumor characterized by its ability to create an immunosuppressive tumor microenvironment. Here, using robust 3D co-culture systems, samples from PDAC patients and murine in vivo models, we described a novel immune evasion mechanism used by PDAC to inhibit the anti-tumor activity of B lymphocytes: We provide evidence that pancreatic cancer suppresses the B cell-specific transcriptional program while enforcing their reprogramming into functional macrophages. Thus, we hypothesize that B cells undergo transdifferentiation under the influence of PDAC, by losing their lymphoid identity and acquiring a myeloid immunosuppressive phenotype. This drastic change is enacted by the loss of Pax5 expression. Importantly, our results showed that the Ex-B cells efficiently become phagocytic and produce soluble proteins that are known to enhance cancer cell survival and proliferation. This suggests that the PDAC-induced B cell to macrophage transdifferentiation pathway is functionally relevant and hence could serve as an immunotherapeutic target.