Related Experiment Video
Updated: Jul 2, 2026
Modeling Oral-Esophageal Squamous Cell Carcinoma in 3D Organoids
Published on: December 23, 2022
Loss of heterozygosity at 6p21 underlying [corrected] HLA class I downregulation in Chinese primary esophageal
1Key Laboratory of Developmental Genes and Human Disease of Education Ministry, Department of Genetics and Developmental Biology, Southeast University Medical School, Nanjing, Jiangsu, China.
Abstract:
Loss or downregulation of human leukocyte antigen (HLA) class I molecules is a widespread mechanism used by tumor cells to avoid tumor recognition by cytotoxic T lymphocytes favoring tumor immune escape. Multiple molecular mechanisms are responsible for these altered HLA class I tumor phenotypes, such as the loss of heterozygosity (LOH) at chromosome region 6p21.3. In this study, we used immunohistological techniques with a highly selective panel of anti-HLA monoclonal antibodies to analyze the expression of HLA class I molecules in 84 formalin-fixed, paraffin-embedded section and 49 frozen-fresh tissues of primary esophageal squamous cell carcinomas (pESCC) from Chinese patients. To elucidate the underlying mechanism of HLA class I loss or downregulation, we also analyzed LOH of previously selected microsatellite markers located in chromosomes 6 and 15 by polymerase chain reaction. DNA was obtained from frozen-fresh tumor tissues and surrounding stroma to define the LOH associated with chromosomes 6p21 and 15q21. Our results showed that HLA-A, HLA-B/C, HLA class I heavy chain, beta2-microglobuline, and HLA class I complex were lost or downregulated in pESCC (P<0.0001), and were moderately associated with the microsatellite alterations in HLA class I gene regions, correlated with patients' age, tumor's location, and stage, and indicated that LOH at 6p21.3 is a frequent mechanism that leads to HLA class I abnormalities in pESCC.
Insights
Tumor cells frequently lose human leukocyte antigen (HLA) class I to evade immune detection. Loss of heterozygosity at chromosome 6p21.3 is a primary driver of these HLA class I abnormalities in esophageal squamous cell carcinoma.
Area of Science:
- Immunology
- Oncology
- Genetics
Background:
- Tumor cells evade immune surveillance by downregulating human leukocyte antigen (HLA) class I molecules.
- Loss of heterozygosity (LOH) at chromosome 6p21.3 is a known mechanism for altered HLA class I expression.
Purpose of the Study:
- To investigate HLA class I expression in primary esophageal squamous cell carcinomas (pESCC).
- To determine the underlying molecular mechanisms, specifically LOH, responsible for HLA class I alterations in pESCC.
Main Methods:
- Immunohistochemical analysis of HLA class I expression using monoclonal antibodies on pESCC tissues.
- Polymerase chain reaction (PCR) to analyze LOH at microsatellite markers on chromosomes 6 and 15 in tumor and stromal DNA.
Main Results:
- Significant loss or downregulation of HLA-A, HLA-B/C, HLA class I heavy chain, beta2-microglobulin, and the HLA class I complex was observed in pESCC (P<0.0001).
- Microsatellite alterations in HLA class I gene regions showed moderate association with HLA class I abnormalities.
- LOH at 6p21.3 was identified as a frequent mechanism leading to HLA class I abnormalities in pESCC, correlated with patient age, tumor location, and stage.
Conclusions:
- HLA class I loss/downregulation is prevalent in pESCC.
- LOH at 6p21.3 is a major mechanism contributing to HLA class I abnormalities in pESCC, impacting tumor immune escape.
Related Concept Videos
01:12Loss of Tumor Suppressor Gene Functions
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
01:21Barrett Esophagus-I: Introduction
This constant acid exposure transforms the esophagus's pink mucosal lining (stratified squamous epithelium) into a type of lining more similar...