ORIGINAL RESEARCH article
Front. Immunol.
Sec. Antigen Presenting Cell Biology
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1641254
PSD3 as a context-dependent modulator of immune landscape and tumor aggressiveness in esophageal squamous cell carcinoma
Provisionally accepted
Shujuan Luo1
Huifang Li2Bangwu Cai1Aiddidar Nurbahati1Hong Cui1Tianyuan Peng1Wei Wang3Qing Liu1Xiaomei Lu1*Shutao Zheng1*- 11.State Key Laboratory of Pathogenesis, Prevention, Treatment of Central Asian High Incidence Diseases, Clinical Medical Research Institute, First Affiliated Hospital of Xinjiang Medical University, Xinjiang Uygur Autonomous Region, Urumqi, 830011, PR China;, Xinjiang Medical University, Urumqi, China
- 2Department of Breast Surgery, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, China
- 3Digestive Internal Medicine, Cancer Hospital of Xinjiang Medical University, Urumqi, China
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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.
Keywords: esophageal squamous cell carcinoma, PSD3, PD-L1, TNFSF18, Tumor Microenvironment, Immune infiltration, biomarker, multiplex immunohistochemistry
Received: 04 Jun 2025; Accepted: 29 Jul 2025.
Copyright: © 2025 Luo, Li, Cai, Nurbahati, Cui, Peng, Wang, Liu, Lu and Zheng. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Xiaomei Lu, 1.State Key Laboratory of Pathogenesis, Prevention, Treatment of Central Asian High Incidence Diseases, Clinical Medical Research Institute, First Affiliated Hospital of Xinjiang Medical University, Xinjiang Uygur Autonomous Region, Urumqi, 830011, PR China;, Xinjiang Medical University, Urumqi, China
Shutao Zheng, 1.State Key Laboratory of Pathogenesis, Prevention, Treatment of Central Asian High Incidence Diseases, Clinical Medical Research Institute, First Affiliated Hospital of Xinjiang Medical University, Xinjiang Uygur Autonomous Region, Urumqi, 830011, PR China;, Xinjiang Medical University, Urumqi, China
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