Elevated SAMD3 expression in T cells predicts improved survival in pancreatic ductal adenocarcinoma patients
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 a...
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| Format: | Article |
| Language: | English |
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Springer
2025-02-01
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| Series: | Cancer Immunology, Immunotherapy |
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| Online Access: | https://doi.org/10.1007/s00262-025-03948-x |
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| _version_ | 1832571671121231872 |
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| author | Lingyi Fu Enliang Zhou Shuo Li Ziteng Li Liyan Wu Xinxin Zhou Lang Tian Bokang Cui |
| author_facet | Lingyi Fu Enliang Zhou Shuo Li Ziteng Li Liyan Wu Xinxin Zhou Lang Tian Bokang Cui |
| author_sort | Lingyi Fu |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-99b33da5a4af47ef970a6fb1b8745a88 |
| institution | Kabale University |
| issn | 1432-0851 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Springer |
| record_format | Article |
| series | Cancer Immunology, Immunotherapy |
| spelling | doaj-art-99b33da5a4af47ef970a6fb1b8745a882025-02-02T12:26:16ZengSpringerCancer Immunology, Immunotherapy1432-08512025-02-0174311310.1007/s00262-025-03948-xElevated SAMD3 expression in T cells predicts improved survival in pancreatic ductal adenocarcinoma patientsLingyi Fu0Enliang Zhou1Shuo Li2Ziteng Li3Liyan Wu4Xinxin Zhou5Lang Tian6Bokang Cui7State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer CenterState Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer CenterState Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer CenterState Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer CenterState Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer CenterState Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer CenterState Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer CenterState Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer CenterAbstract 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.https://doi.org/10.1007/s00262-025-03948-xPancreatic ductal adenocarcinomaT cellSAMD3Single-cell RNA sequencing |
| spellingShingle | Lingyi Fu Enliang Zhou Shuo Li Ziteng Li Liyan Wu Xinxin Zhou Lang Tian Bokang Cui Elevated SAMD3 expression in T cells predicts improved survival in pancreatic ductal adenocarcinoma patients Cancer Immunology, Immunotherapy Pancreatic ductal adenocarcinoma T cell SAMD3 Single-cell RNA sequencing |
| title | Elevated SAMD3 expression in T cells predicts improved survival in pancreatic ductal adenocarcinoma patients |
| title_full | Elevated SAMD3 expression in T cells predicts improved survival in pancreatic ductal adenocarcinoma patients |
| title_fullStr | Elevated SAMD3 expression in T cells predicts improved survival in pancreatic ductal adenocarcinoma patients |
| title_full_unstemmed | Elevated SAMD3 expression in T cells predicts improved survival in pancreatic ductal adenocarcinoma patients |
| title_short | Elevated SAMD3 expression in T cells predicts improved survival in pancreatic ductal adenocarcinoma patients |
| title_sort | elevated samd3 expression in t cells predicts improved survival in pancreatic ductal adenocarcinoma patients |
| topic | Pancreatic ductal adenocarcinoma T cell SAMD3 Single-cell RNA sequencing |
| url | https://doi.org/10.1007/s00262-025-03948-x |
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