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Objective <p>Pancreatic ductal adenocarcinoma (PDAC) has an immune-suppressive tumor microenvironment that contributes to resistance to immunotherapy. This study aimed to demonstrate that elevated <i>sterile alpha motif domain-containing protein 3</i> (<i>SAMD3</i>) expression in effector CD8<sup>+</sup> T cells was associated with improved survival in PDAC patients.</p> Design <p>We investigated the heterogeneity and gene expression profiles of T cells using a single-cell RNA sequencing (sc-RNA-seq) dataset comprised of human PDAC samples. <i>SAMD3</i> mRNA expression was further evaluated in a tumor-specific OT-I/ovalbumin (OVA) mouse model. SAMD3 levels and their clinical significance were evaluated via immunohistochemistry (IHC) analysis.</p> Results <p><i>SAMD3</i> was highly expressed in cytotoxic CD8<sup>+</sup> T cells, with expression significantly downregulated during T cell exhaustion. <i>SAMD3</i> levels were positively correlated with CD8<sup>+</sup> T cell function. In PDAC patients, high SAMD3 levels in T cells were associated with improved overall survival (OS), disease-free survival (DFS), and T cell infiltration. A patient exhibiting partial response to combination immunotherapy also showed high SAMD3 levels in T cells.</p> Conclusion <p>SAMD3 is a biomarker of T cell function, with elevated expression in T cells predicting improved survival. These findings highlight the potential of precision immunotherapy approaches for treating PDAC.</p>

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Elevated SAMD3 expression in T cells predicts improved survival in pancreatic ductal adenocarcinoma patients

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年2月1日

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  • Lingyi Fu,
  • Enliang Zhou,
  • Shuo Li,
  • Ziteng Li,
  • Liyan Wu,
  • Xinxin Zhou,
  • Lang Tian,
  • Bokang Cui

摘要

Objective

Pancreatic ductal adenocarcinoma (PDAC) has an immune-suppressive tumor microenvironment that contributes to resistance to immunotherapy. This study aimed to demonstrate that elevated sterile alpha motif domain-containing protein 3 (SAMD3) expression in effector CD8+ T cells was associated with improved survival in PDAC patients.

Design

We investigated the heterogeneity and gene expression profiles of T cells using a single-cell RNA sequencing (sc-RNA-seq) dataset comprised of human PDAC samples. SAMD3 mRNA expression was further evaluated in a tumor-specific OT-I/ovalbumin (OVA) mouse model. SAMD3 levels and their clinical significance were evaluated via immunohistochemistry (IHC) analysis.

Results

SAMD3 was highly expressed in cytotoxic CD8+ T cells, with expression significantly downregulated during T cell exhaustion. SAMD3 levels were positively correlated with CD8+ T cell function. In PDAC patients, high SAMD3 levels in T cells were associated with improved overall survival (OS), disease-free survival (DFS), and T cell infiltration. A patient exhibiting partial response to combination immunotherapy also showed high SAMD3 levels in T cells.

Conclusion

SAMD3 is a biomarker of T cell function, with elevated expression in T cells predicting improved survival. These findings highlight the potential of precision immunotherapy approaches for treating PDAC.