CD103(+) T Cells Eliminate Damaged Alveolar Epithelial Type II Cells Under Oxidative Stress to Prevent Lung Tumorigenesis.

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.