CD103+ T Cells Eliminate Damaged Alveolar Epithelial Type II Cells Under Oxidative Stress to Prevent Lung Tumorigenesis
Abstract The nexus between aging‐associated immune deteriorations and tumorigenesis of lung cancers remains elusive. In a mouse model with Med23 depletion in T cells (Med23 −/−), it is found a strong association between the decline of CD103+ T cells and spontaneous alveolar epithelial type II cell (...
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| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wiley
2025-07-01
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| Series: | Advanced Science |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/advs.202503557 |
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| Summary: | Abstract The nexus between aging‐associated immune deteriorations and tumorigenesis of lung cancers remains elusive. In a mouse model with Med23 depletion in T cells (Med23 −/−), it is found a strong association between the decline of CD103+ T cells and spontaneous alveolar epithelial type II cell (AT2 cell)‐originated lung adenocarcinomas. The reduction of CD103+ T cells in the lung results in an accumulation of AT2 cells bearing oxidative damages, which appears to be the major origin of the lung adenocarcinoma. Functional experiments reveal CD103+ T cells can eradicate oxidative‐damage‐bearing AT2 cells as well as ROS‐dependent, KRAS (G12D)‐driven tumorigenesis. In vitro co‐cultures prove CD103+ T cells, especially CD103+ CD8+ T cells, exhibit a killing capacity that matches the oxidative stress level in the target cells. In aged animals, it is found the abundance of CD103+ CD8+ T cells in the lung declines with age, accompanied by an accumulation of oxidative‐damage‐bearing AT2 cells. Collectively, the study establishes the vital function of CD103+ T cells in surveilling epithelial cells under oxidative stress to prevent malignancies, and unravels a potential immuno‐dysregulation in the aged lung which contributes to tumorigenesis. |
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| ISSN: | 2198-3844 |