PSD3 as a context-dependent modulator of immune landscape and tumor aggressiveness in esophageal squamous cell carcinoma
In this study, we investigated PSD3, CD274 (PD-L1), and TNFSF18 as potential immune-related biomarkers in esophageal squamous cell carcinoma (ESCC) using integrative transcriptomic and experimental approaches. CD274 and TNFSF18 were consistently up-regulated in ESCC across both TCGA and GEO datasets...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2025-08-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1641254/full |
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| author | Shujuan Luo Huifang Li Bangwu Cai Aididar Nurbahati Hong Cui Tianyuan Peng Wei Wang Qing Liu Xiaomei Lu Shutao Zheng |
| author_facet | Shujuan Luo Huifang Li Bangwu Cai Aididar Nurbahati Hong Cui Tianyuan Peng Wei Wang Qing Liu Xiaomei Lu Shutao Zheng |
| author_sort | Shujuan Luo |
| collection | DOAJ |
| description | In this study, we investigated PSD3, CD274 (PD-L1), and TNFSF18 as potential immune-related biomarkers in esophageal squamous cell carcinoma (ESCC) using integrative transcriptomic and experimental approaches. CD274 and TNFSF18 were consistently up-regulated in ESCC across both TCGA and GEO datasets, while PSD3 showed significantly higher expression in TCGA but no significant difference in the GEO cohort. Only PSD3 demonstrated a significant association with overall survival, with higher expression correlating with improved prognosis. Interestingly, despite its favorable prognostic value, PSD3 functionally promoted ESCC cell proliferation, invasion, and migration in vitro, while inversely regulating PD-L1 expression. Conversely, heterozygous knockout of PD-L1 in KYSE150 cells impaired tumor aggressiveness. Co-immunoprecipitation revealed a direct physical interaction between PSD3 and PD-L1, suggesting a regulatory axis with implications for immune evasion. These findings position PSD3 as a context-dependent immuno-oncogenic factor and a potential therapeutic target in ESCC. |
| format | Article |
| id | doaj-art-b0e3bd4d7b024709993be491e1c40a19 |
| institution | Kabale University |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj-art-b0e3bd4d7b024709993be491e1c40a192025-08-20T04:01:02ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-08-011610.3389/fimmu.2025.16412541641254PSD3 as a context-dependent modulator of immune landscape and tumor aggressiveness in esophageal squamous cell carcinomaShujuan Luo0Huifang Li1Bangwu Cai2Aididar Nurbahati3Hong Cui4Tianyuan Peng5Wei Wang6Qing Liu7Xiaomei Lu8Shutao Zheng9State Key Laboratory of Pathogenesis, Prevention, Treatment of Central Asian High Incidence Diseases, Clinical Medical Research Institute, First Affiliated Hospital of Xinjiang Medical University, Urumqi, ChinaDepartment of Breast Surgery, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, ChinaState Key Laboratory of Pathogenesis, Prevention, Treatment of Central Asian High Incidence Diseases, Clinical Medical Research Institute, First Affiliated Hospital of Xinjiang Medical University, Urumqi, ChinaState Key Laboratory of Pathogenesis, Prevention, Treatment of Central Asian High Incidence Diseases, Clinical Medical Research Institute, First Affiliated Hospital of Xinjiang Medical University, Urumqi, ChinaState Key Laboratory of Pathogenesis, Prevention, Treatment of Central Asian High Incidence Diseases, Clinical Medical Research Institute, First Affiliated Hospital of Xinjiang Medical University, Urumqi, ChinaState Key Laboratory of Pathogenesis, Prevention, Treatment of Central Asian High Incidence Diseases, Clinical Medical Research Institute, First Affiliated Hospital of Xinjiang Medical University, Urumqi, ChinaDepartment of Digestive Internal Medicine, The Affiliated Tumor Hospital of Xinjiang Medical University, Urumqi, Xinjiang, ChinaState Key Laboratory of Pathogenesis, Prevention, Treatment of Central Asian High Incidence Diseases, Clinical Medical Research Institute, First Affiliated Hospital of Xinjiang Medical University, Urumqi, ChinaState Key Laboratory of Pathogenesis, Prevention, Treatment of Central Asian High Incidence Diseases, Clinical Medical Research Institute, First Affiliated Hospital of Xinjiang Medical University, Urumqi, ChinaState Key Laboratory of Pathogenesis, Prevention, Treatment of Central Asian High Incidence Diseases, Clinical Medical Research Institute, First Affiliated Hospital of Xinjiang Medical University, Urumqi, ChinaIn this study, we investigated PSD3, CD274 (PD-L1), and TNFSF18 as potential immune-related biomarkers in esophageal squamous cell carcinoma (ESCC) using integrative transcriptomic and experimental approaches. CD274 and TNFSF18 were consistently up-regulated in ESCC across both TCGA and GEO datasets, while PSD3 showed significantly higher expression in TCGA but no significant difference in the GEO cohort. Only PSD3 demonstrated a significant association with overall survival, with higher expression correlating with improved prognosis. Interestingly, despite its favorable prognostic value, PSD3 functionally promoted ESCC cell proliferation, invasion, and migration in vitro, while inversely regulating PD-L1 expression. Conversely, heterozygous knockout of PD-L1 in KYSE150 cells impaired tumor aggressiveness. Co-immunoprecipitation revealed a direct physical interaction between PSD3 and PD-L1, suggesting a regulatory axis with implications for immune evasion. These findings position PSD3 as a context-dependent immuno-oncogenic factor and a potential therapeutic target in ESCC.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1641254/fullesophageal squamous cell carcinomaPSD3PD-L1TNFSF18tumor microenvironmentimmune infiltration |
| spellingShingle | Shujuan Luo Huifang Li Bangwu Cai Aididar Nurbahati Hong Cui Tianyuan Peng Wei Wang Qing Liu Xiaomei Lu Shutao Zheng PSD3 as a context-dependent modulator of immune landscape and tumor aggressiveness in esophageal squamous cell carcinoma Frontiers in Immunology esophageal squamous cell carcinoma PSD3 PD-L1 TNFSF18 tumor microenvironment immune infiltration |
| title | PSD3 as a context-dependent modulator of immune landscape and tumor aggressiveness in esophageal squamous cell carcinoma |
| title_full | PSD3 as a context-dependent modulator of immune landscape and tumor aggressiveness in esophageal squamous cell carcinoma |
| title_fullStr | PSD3 as a context-dependent modulator of immune landscape and tumor aggressiveness in esophageal squamous cell carcinoma |
| title_full_unstemmed | PSD3 as a context-dependent modulator of immune landscape and tumor aggressiveness in esophageal squamous cell carcinoma |
| title_short | PSD3 as a context-dependent modulator of immune landscape and tumor aggressiveness in esophageal squamous cell carcinoma |
| title_sort | psd3 as a context dependent modulator of immune landscape and tumor aggressiveness in esophageal squamous cell carcinoma |
| topic | esophageal squamous cell carcinoma PSD3 PD-L1 TNFSF18 tumor microenvironment immune infiltration |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1641254/full |
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