Myeloid-Derived Suppressor Cells Down-Regulate L-Selectin Expression on CD4+ and CD8+ T Cells

摘要: Effective cell-mediated antitumor immunity requires the activation of tumor-reactive T cells and trafficking activated to tumor sites. These processes involve extravasation lymphocytes from blood lymphatics, their homing lymph nodes tumors. L-selectin (CD62L) is an important molecule in these processes. It directs naive peripheral where they become it traffics inflammatory environments, such as Individuals with advanced cancer are immune suppressed due myeloid-derived suppressor (MDSC), a population immature myeloid that accumulate high levels response tumor-secreted proinflammatory factors. We now demonstrate reduction cell commonly seen individuals inversely correlates MDSC levels. Three lines evidence directly down-regulate on cells: 1) cocultured tumor-induced have reduced L-selectin; 2) tumor-free aged mice elevated L-selectin, 3) peritoneal exudate treated plasminogen activator urokinase elevate L-selectin. likely through plasma membrane expression ADAM17 (a disintegrin metalloproteinase domain 17), enzyme cleaves ectodomain Therefore, cells, decreasing ability home sites would be activated. This another mechanism by which inhibit immunity.