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

IF 4.6 2区医学 Q2 IMMUNOLOGY

Cancer Immunology, Immunotherapy Pub Date : 2025-02-01 DOI:10.1007/s00262-025-03948-x

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

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引用次数: 0

Abstract

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.

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来源期刊

Cancer Immunology, Immunotherapy 医学-免疫学

CiteScore

10.50

自引率

1.70%

发文量

207

审稿时长

1 months

期刊介绍： Cancer Immunology, Immunotherapy has the basic aim of keeping readers informed of the latest research results in the fields of oncology and immunology. As knowledge expands, the scope of the journal has broadened to include more of the progress being made in the areas of biology concerned with biological response modifiers. This helps keep readers up to date on the latest advances in our understanding of tumor-host interactions. The journal publishes short editorials including "position papers," general reviews, original articles, and short communications, providing a forum for the most current experimental and clinical advances in tumor immunology.