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Genetic Association Between Immune Cells and Oral Cancer: A Mendelian Randomization Study
Jialiang Li1, Fanyu Peng2, Quan Ma1
1Department of Stomatology, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School.
Journal of Stomatology, Oral and Maxillofacial Surgery
|July 29, 2026
Summary
This study reveals immune cell phenotypes and cytokines causally linked to oral cancer risk. Activated CD4 Tregs and CCL5 may increase oral cancer risk, while resting CD4 Tregs may decrease it.
Area of Science:
- Immunology
- Oncology
- Genetics
Background:
- Oral cancer incidence is rising, with the tumor microenvironment playing a crucial role.
- Causal links between immune cell phenotypes, cytokines, and oral cancer are not fully understood.
Purpose of the Study:
- To investigate the causal relationships between immune cells, cytokines, and oral cancer using Mendelian randomization.
- To identify potential therapeutic targets for oral cancer treatment.
Main Methods:
- Utilized large-scale genome-wide association study (GWAS) data.
- Performed bidirectional Mendelian randomization analysis on 731 immune cell phenotypes and 41 cytokines.
- Validated findings using single-cell RNA sequencing data.
Main Results:
- Identified causal links between 29 immune cell phenotypes and oral cancer.
- Activated and secretory CD4 Tregs were positively correlated with oral cancer risk.
- Resting CD4 Tregs showed a negative correlation with oral cancer risk.
- Oral cancer influenced 41 immune cell phenotypes.
- Elevated RANTES (CCL5) increased oral cancer risk; oral cancer raised beta-nerve growth factor (NGF) levels.
Conclusions:
- Established multiple causal relationships between immune cell phenotypes and oral cancer.
- Activated/secretory CD4 Tregs may increase oral cancer risk.
- CCL5 and NGF are identified as potentially significant cytokines in oral tumorigenesis, suggesting therapeutic potential.
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