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<p>Pancreatic ductal adenocarcinoma (PDAC) remains a highly aggressive malignancy driven by rapid metastasis and a profoundly immunosuppressive microenvironment. While the surface glycoprotein CD52 is a known immunoregulator, its precise role in solid tumors remains controversial, partly due to its broad expression across diverse cell populations and its compartment-specific functions within the tumor microenvironment. In this study, we utilized integrated single-cell RNA sequencing (scRNA-seq), functional assays, and compartment-specific clinical validation to elucidate the tumor-intrinsic functions of CD52 in PDAC. We identified a highly plastic, restricted subpopulation of CD52-high malignant epithelial cells that actively drives metastasis initiation by enhancing cellular invasive capacity. Concurrently, we demonstrated that tumor-derived CD52 orchestrated a multi-layered immunosuppressive network that attenuates CD8 + T cell cytotoxicity, facilitating early immune evasion. Furthermore, by systematically separating expression sources, our clinical validation established that tumor-derived CD52 is a prognostic indicator of poor patient survival. These findings characterize CD52 as a critical, tumor-intrinsic driver of PDAC progression, highlighting its value as a prognostic biomarker and a therapy target in combination with immune checkpoint blockade to overcome innate therapeutic resistance in PDAC.</p>

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Integrated scRNA-Seq and functional profiling reveal CD52 as a driver of pancreatic ductal adenocarcinoma metastasis and immunosuppression

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年6月27日

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  • Zeyu Zhang,
  • Jinxin Tao,
  • Yifan Fu,
  • Yi Dong,
  • Yuanyang Wang,
  • Menggang Zhang,
  • Liyuan Ye,
  • Jiangdong Qiu,
  • Yueze Liu,
  • Hao Chen,
  • Jianchun Xiao,
  • Hua Huang,
  • Zhe Cao,
  • Gang Yang,
  • Taiping Zhang

摘要

Pancreatic ductal adenocarcinoma (PDAC) remains a highly aggressive malignancy driven by rapid metastasis and a profoundly immunosuppressive microenvironment. While the surface glycoprotein CD52 is a known immunoregulator, its precise role in solid tumors remains controversial, partly due to its broad expression across diverse cell populations and its compartment-specific functions within the tumor microenvironment. In this study, we utilized integrated single-cell RNA sequencing (scRNA-seq), functional assays, and compartment-specific clinical validation to elucidate the tumor-intrinsic functions of CD52 in PDAC. We identified a highly plastic, restricted subpopulation of CD52-high malignant epithelial cells that actively drives metastasis initiation by enhancing cellular invasive capacity. Concurrently, we demonstrated that tumor-derived CD52 orchestrated a multi-layered immunosuppressive network that attenuates CD8 + T cell cytotoxicity, facilitating early immune evasion. Furthermore, by systematically separating expression sources, our clinical validation established that tumor-derived CD52 is a prognostic indicator of poor patient survival. These findings characterize CD52 as a critical, tumor-intrinsic driver of PDAC progression, highlighting its value as a prognostic biomarker and a therapy target in combination with immune checkpoint blockade to overcome innate therapeutic resistance in PDAC.