085 Senescent dendritic cells drive ROS-induced DNA damage in CTCL

Progressive DNA damage and worsening aneuploidy are associated with the development of highly aggressive CTCL. We immunostained MF skin lesions for phosphorylated double-strand break repair genes γH2AX 53BP1 phosphorylated/activated ATM (pATM) found that ongoing breaks were frequent within malignant T cells even in clinically stable lesions. IL-6, a product senescent cells, is second most expressed cytokine MF. Immunostaining demonstrated senescence marker p21Cip1 was increased stage specific manner localized to OX40L+CD40L+ dendritic cells. These DC also thioredoxin (TXN), indicating production reactive oxygen species (ROS) clustered closely together benign ROS by known drive ROS-induced neighboring therefore near evidence oxidative stress (TXN) (γH2AX). increase experiencing DC. Malignant primarily affected but some CD7+ infiltrating showed later (IIA, IIB). Our results suggest produced induces may cell transformation tumor progression. studies possible role senolytic therapies treatment