Investigating the immunological function of alpha-2-glycoprotein 1, zinc-binding in regulating tumor response in the breast cancer microenvironment.
Alpha-2-glycoprotein 1, zinc-binding
Androgen receptor
Breast cancer
Macrophage differentiation
Microenvironment
Tumor immunity
Journal
Cancer immunology, immunotherapy : CII
ISSN: 1432-0851
Titre abrégé: Cancer Immunol Immunother
Pays: Germany
ID NLM: 8605732
Informations de publication
Date de publication:
13 Feb 2024
13 Feb 2024
Historique:
received:
11
09
2023
accepted:
07
01
2024
medline:
13
2
2024
pubmed:
13
2
2024
entrez:
13
2
2024
Statut:
epublish
Résumé
Alpha-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. Using 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. AZGP1 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. ZAG is suggested to be a novel immunoregulatory factor affecting the Mφ phenotype in breast cancer tissues.
Sections du résumé
BACKGROUND
BACKGROUND
Alpha-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.
METHODS
METHODS
Using 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.
RESULTS
RESULTS
AZGP1 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.
CONCLUSION
CONCLUSIONS
ZAG is suggested to be a novel immunoregulatory factor affecting the Mφ phenotype in breast cancer tissues.
Identifiants
pubmed: 38349455
doi: 10.1007/s00262-024-03629-1
pii: 10.1007/s00262-024-03629-1
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
42Subventions
Organisme : Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology, Japan
ID : 20K22856
Organisme : Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology, Japan
ID : 18K16266
Informations de copyright
© 2024. The Author(s).
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