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Published on: February 8, 2020
Structure, expression and function of HLA-G in renal cell carcinoma
Barbara Seliger1, Gerald Schlaf
1Martin Luther University Halle-Wittenberg, Institute of Medical Immunology, Magdeburger Strasse 2, 06112 Halle, Germany. Barbara.Seliger@medizin.uni-halle.de
Seminars in Cancer Biology
|August 21, 2007
Summary
Renal cell carcinoma (RCC) frequently expresses HLA-G, a molecule that helps tumors evade immune detection. This immune escape mechanism impacts the development of T and NK cell-based immunotherapies for RCC.
Area of Science:
- Immunology
- Oncology
- Molecular Biology
Background:
- Tumors employ immune evasion strategies, including altered Human Leukocyte Antigen (HLA) expression.
- Renal cell carcinoma (RCC) exhibits aberrant MHC class surface expression, aiding immune escape.
Purpose of the Study:
- To review the structure, expression, regulation, and functional consequences of HLA-G in RCC.
- To understand HLA-G's role as an immune escape mechanism in RCC.
Main Methods:
- Review of literature on HLA-G structure, polymorphism, mRNA, and protein expression in RCC.
- Analysis of HLA-G regulation by tumor microenvironment, interferons, IL-10, gangliosides, and methylation.
- Functional studies using NK cells, LAK cells, and CD8+ CTLs to assess HLA-G's impact on RCC cell lysis.
Main Results:
- Heterogeneous HLA-G mRNA/protein expression found in RCC, absent in normal kidney epithelium.
- RCC exhibits a relatively high frequency of HLA-G expression compared to other tumors.
- HLA-G expression prevents lysis of RCC cells by NK and T cells, while HLA-G-negative cells are recognized.
Conclusions:
- HLA-G is a significant immune escape mechanism in human RCC.
- Tumor microenvironment and endothelium likely regulate HLA-G expression in RCC.
- Understanding HLA-G's role is crucial for designing effective T and NK cell-based immunotherapies for RCC.
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