Tissue-resident memory T (T_RM) cells are a unique T cell population that exhibits long-term persistence in non-lymphoid tissues. To establish local residency, T_RM progenitors gradually acquire distinct functional and migratory features including the upregulation of molecules for tissue retention such as CD103 and CD69. Recent studies have confirmed that T_RM cells are more efficient protecting tissue from recurrent infections as compared to memory T cells in circulation.

In a study published in Advanced Science, a research team led by Prof. LIU Xiaolong from the Center for Excellence in Molecular Cell Science of the Chinese Academy of Sciences revealed the distinct function of CD103⁺ T cells in lung tumorigenesis and identified a potential immuno-dysregulation in the aged lung which contributes to tumorigenesis.

Researchers found that the aged lung exhibited a specific decline of CD103⁺ T cells which belong to the tissue-resident T cell compartment. To study whether the decline of these cells alters tissue fitness, they used a mouse model with Med23 depletion in T cells (Med23^-/-), and found a strong association between the decline of CD103⁺ T cells and spontaneous alveolar epithelial type II (AT2) cell-originated lung adenocarcinomas.

Then, researchers mapped the major pro-tumorigenic event in the Med23^-/- AT2 cells to the oxidative stress. Functional experiments further proved that the CD103⁺ T cells eliminated AT2 cells bearing oxidative stress to prevent ROS-dependent tumorigenesis. Also, researchers found a significant correlation between the increased oxidative-stress-bearing AT2 cells and the decreased formation of lung CD103⁺ T cells in human lung samples.

This study demonstrates the function of CD103⁺ T cells in surveilling oxidative-stressed epithelial cells to prevent malignancies, and underscores the specific decline in CD103⁺ T cells as a key feature in the aged lung, which provides novel insights into the regional immune regulations against malignancies arising from oxidative stress.