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Exploring the Link Between Stress-Induced Naive T-Cells and Esophageal Squamous Cell Carcinoma Risk: A Multi-Omics
Jingge Cheng1, Dengfeng Zhang2, Longyu Zhu1
1The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, China.
Annals of Surgical Oncology
|November 4, 2025
Summary
Increased naive T-lymphocyte abundance causally links to higher esophageal cancer risk. These T-cells become anergic in the tumor microenvironment, impairing anti-cancer immunity and promoting cancer progression.
Area of Science:
- Immunology
- Oncology
- Genetics
Background:
- Immune homeostasis is crucial for preventing cancer.
- Naïve T-lymphocytes are key players in anti-tumor responses.
- Understanding their role in esophageal carcinogenesis is vital.
Purpose of the Study:
- To investigate the causal relationship between T-cell subsets and esophageal squamous cell carcinoma.
- To elucidate the mechanistic link between naïve T-cells and esophageal cancer development.
Main Methods:
- Utilized a bidirectional two-sample Mendelian randomization approach.
- Analyzed genome-wide summary statistics from large cancer and immunophenotyping cohorts.
- Employed single-cell transcriptional profiling for mechanistic insights.
Main Results:
- Found a significant causal effect of increased naïve T-cell abundance on esophageal cancer risk (OR 1.14, P=0.021).
- Observed tumor-infiltrating naïve T-cells in a quiescent state with suppressed differentiation.
- Linked this functional impairment to reduced immunoediting and immune evasion.
Conclusions:
- Naïve T-cell abundance is a novel causal risk factor for esophageal squamous cell carcinoma.
- Metabolic silencing and differentiation blockade in the tumor niche drive T-cell dysfunction.
- Targeting T-cell metabolism may offer new therapeutic strategies against immune evasion in esophageal cancer.
