ArticleCancer immunology, immunotherapy : CII2024
Investigating the immunological function of alpha-2-glycoprotein 1, zinc-binding in regulating tumor response in the breast cancer microenvironment.
Article in Cancer immunology, immunotherapy : CII, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed, 6 citations in OpenAlex.
- O-GlcNAcylation of AZGP1 regulates M1/M2 macrophage polarization in diabetic periodontitis.Odontology · 2026Article
- AZGP1 deficiency promotes chronic kidney fibrosis in aging mice.American journal of clinical and experimental urology · 2026Article
- Loss of EHMT2 enhances NK cell-driven anti-tumor immunity through TGF-β1 suppression.EMBO molecular medicine · 2026Article
- HallmarkGraph: a cancer hallmark informed graph neural network for classifying hierarchical tumor subtypes.Bioinformatics (Oxford, England) · 2025Article
- Longitudinal proteomic analysis of pathophysiology in plasma and bronchoalveolar lavage fluid of patients with ARDS.Journal of intensive care · 2025Article
- Spatial gene expression profiling identifies prognostic features of residual tumors after neoadjuvant chemotherapy in triple-negative breast cancer.Frontiers in oncology · 2025Article
- Targeting mitochondrial damage: shining a new light on immunotherapy.Frontiers in immunology · 2024Review
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Authors and funding
14 authors at 7 institutions in 2 countries.
Funding
Abstract
backgroundAlpha-2-glycoprotein 1, zinc-binding (ZAG), a secreted protein encoded by the AZGP1 gene, is structurally similar to HLA class I. Despite its presumed immunological function, little is known about its role in tumor immunity. In this study, we thus aimed to determine the relationship between the expression of AZGP1/ZAG and the immunological profiles of breast cancer tissues at both the gene and protein level.
methodsUsing a publicly available gene expression dataset from a large-scale breast cancer cohort, we conducted gene set enrichment analysis (GSEA) to screen the biological processes associated with AZGP1. We analyzed the correlation between AZGP1 expression and immune cell composition in breast cancer tissues, estimated using CIBERSORTx. Previously, we evaluated the infiltration of 11 types of immune cells for 45 breast cancer tissues using flow cytometry (FCM). ZAG expression was evaluated by immunohistochemistry on these specimens and analyzed for its relationship with immune cell infiltration. The action of ZAG in M1/M2 polarization models using primary cultures of human peripheral blood mononuclear cells (PBMC)-derived macrophage (Mφ) was analyzed based on the expression of M1/M2 markers (CD86, CD80/CD163, MRC1) and HLA class I/II by FCM.
resultsAZGP1 expression was negatively correlated with multiple immunological processes and specific immune cell infiltration including Mφ M1 using GSEA and CIBERSORTx. ZAG expression was associated with decreased infiltration of monocytes/macrophages, non-classical monocytes, and myeloid-derived suppressor cells in tumor tissues assessed using FCM. In in vitro analyses, ZAG decreased the expression of CD80, CD163, MRC1, and HLA classes I/II in the M1 polarization model and the expression of CD163 and MRC1 in the M2 polarization model.
conclusionZAG is suggested to be a novel immunoregulatory factor affecting the Mφ phenotype in breast cancer tissues.
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