Impaired CD103+ T cell accumulation facilitates oxidative damage induced lung adenocarcinoma

Immune microenvironment plays essential roles in tumor progression. The molecular mechanism underlying the regulation of immune surveillance in tumor initiation remains to be elucidated. Here we show that mice with T cell-specific deletion of the mediator subunit Med23 develops the alveolar epithelial type II cells (AT2 cells) originated lung adenocarcinoma, and such lung tumors displays an increased mutation frequency of oncogenes. Notably, the tumorigenesis of lung adenocarcinoma in Med23-deficient mice is promoted by the accumulation of AT2 cells under oxidative stress and oxidative DNA damage. Antioxidant treatment partially rescues spontaneous lung adenocarcinoma in Med23-deficient mice. Moreover, we find that loss of MED23 impairs the accumulation of lung CD103+ T cells, usually recognized as tissue resident T cells. CD103+ T cells have the ability to scavenge AT2 cells bearing oxidative DNA damage and prevent the tumorigenesis of lung adenocarcinoma. Mechanistically, CD103+ T cells predispose cells with high-level of oxidative stress to apoptosis. Collectively, our study finds MED23 is the key regulator of CD103+ T cell in lungs and reveals the immunosurveillance of CD103+ T cells in tumorigenesis. Overall design: To investigate the tumor type and charateristics of the spontaneous lung tumors in mice with Med23 deletion in T cells, lung tumors and adjacent normal tissues were analyzed using RNA-seq. To investigate the phenotype of AT2 cells before tumorigenesis in mice with Med23 deletion in T cells, AT2 cells were isolated by Fluorescence-activated cell sorting (FACS) and analyzed using RNA-seq.