ArticleThe Journal of clinical investigation2023
SCCA1/SERPINB3 suppresses antitumor immunity and blunts therapy-induced T cell responses via STAT-dependent chemokine production.
Article in The Journal of clinical investigation, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 31 citations in OpenAlex.
- H3K18la in periodontal ligament fibroblasts regulates immune niches and alveolar bone remodeling under mechanical loads.International journal of oral science · 2026Article
- Integrated Immune Escape in Cervical Cancer: HLA-I Dysfunction and Immune Checkpoint Signaling.International journal of molecular sciences · 2026Review
- Regulatory mechanism of the RNF168-SCCA1-MYH9 signaling axis in the response of ulcerative colitis.Journal of gastroenterology · 2026Article
- LAMC2Cancer science · 2026Article
- Preoperative prediction of the need for postoperative adjuvant therapy in stage IB cervical cancer using tumor size measured on magnetic resonance imaging and serum squamous cell carcinoma antigen levels.AJOG global reports · 2026Article
- Hypomethylation of GNA15 Promotes Pancreatic Ductal Adenocarcinoma Progression and Macrophage M2 Polarization via STAT3-CXCL8 Axis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Spatiotemporal dynamics of radioresistance: decoding macrophage-driven radioprotective niches through temporal-spatial reprogramming.Molecular cancer · 2026Review
- Signatures of Pancreatic Ductal Adenocarcinoma Uncovered by Integrative Multi-Omics Analysis.Cancers · 2026Article
- Spatial analysis of HPV-associated cervical intraepithelial neoplastic tissues demonstrate distinct immune signatures associated with cervical cancer progression.The Journal of pathology · 2026Article
- Transcriptomic characterization of key psoriasis-associated genes based on single-cell RNA-seq and machine learning.PloS one · 2026Article
- Myeloid-Derived Suppressor Cells and Radiotherapy: Regulation and Clinical Implications.Journal of Cancer · 2026Review
- SERPINB3 enhances NPM1 sumoylation via inhibiting SENP3's activity and promotes lung tumorigenesis.Cell death & disease · 2025Article
- A chemokine-based prognostic model featuring CXCL8, ITGA5, BACE2, CCR7, CERS4, and MEI1 for cervical cancer.European journal of medical research · 2025Article
- Targeting SERPINB3-MAPK axis-mediated cuproptosis resistance enhances the response to antitumor immunotherapy.Molecular cancer · 2025Article
- Integrated multi-omics analysis reveals PTM networks as key regulators of colorectal cancer progression and immune evasion.Discover oncology · 2025Article
- SerpinB3/Protease Activated Receptor-2 Axis Is Essential for SARS CoV-2 Infection.ACS infectious diseases · 2025Article
- MYC/TET3-Regulated TMEM65 Activates OXPHOS-SERPINB3 Pathway to Promote Progression and Cisplatin Resistance in Triple-Negative Breast Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Serum SERPINB3/4 in Moderate-to-Severe Prurigo Nodularis: A Potential Biomarker for Disease Severity and Eosinophil-Related Parameters.Immunity, inflammation and disease · 2025Article
- Tumor-derived exosomal CCT6A serves as a matchmaker introducing chemokines to tumor-associated macrophages in pancreatic ductal adenocarcinoma.Cell death & disease · 2025Article
- Navigating established and emerging biomarkers for immune checkpoint inhibitor therapy.Cancer cell · 2025Review
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Authors and funding
19 authors at 3 institutions in 2 countries.
Funding
Abstract
Patients with cancer who have high serum levels of squamous cell carcinoma antigen 1 (SCCA1, now referred to as SERPINB3) commonly experience treatment resistance and have a poor prognosis. Despite being a clinical biomarker, the modulation of SERPINB3 in tumor immunity is poorly understood. We found positive correlations of SERPINB3 with CXCL1, CXCL8 (CXCL8/9), S100A8, and S100A9 (S100A8/A9) myeloid cell infiltration through RNA-Seq analysis of human primary cervical tumors. Induction of SERPINB3 resulted in increased CXCL1/8 and S100A8/A9 expression, which promoted monocyte and myeloid-derived suppressor cell (MDSC) migration in vitro. In mouse models, Serpinb3a tumors showed increased MDSC and tumor-associated macrophage (TAM) infiltration, contributing to T cell inhibition, and this was further augmented upon radiation. Intratumoral knockdown (KD) of Serpinb3a resulted in tumor growth inhibition and reduced CXCL1 and S100A8/A expression and MDSC and M2 macrophage infiltration. These changes led to enhanced cytotoxic T cell function and sensitized tumors to radiotherapy (RT). We further revealed that SERPINB3 promoted STAT-dependent expression of chemokines, whereby inhibition of STAT activation by ruxolitinib or siRNA abrogated CXCL1/8 and S100A8/ A9 expression in SERPINB3 cells. Patients with elevated pretreatment SCCA levels and high phosphorylated STAT3 (p-STAT3) had increased intratumoral CD11b+ myeloid cells compared with patients with low SCCA levels and p-STAT3, who had improved overall survival after RT. These findings provide a preclinical rationale for targeting SERPINB3 in tumors to counteract immunosuppression and improve the response to RT.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.