NF-κB Hyperactivation in Tumor Tissues Allows Tumor-Selective Reprogramming of the Chemokine Microenvironment to Enhance the Recruitment of Cytolytic T Effector Cells

摘要: Tumor infiltration with effector CD8(+) T cells (T(eff)) predicts longer recurrence-free survival in many types of human cancer, illustrating the broad significance T(eff) for effective immunosurveillance. Colorectal tumors reduced accumulation express low levels T(eff)-attracting chemokines such as CXCL10/IP10 and CCL5/RANTES. In this study, we investigated feasibility enhancing tumor production a cancer therapeutic strategy using tissue explant culture system to analyze chemokine induction intact tissues. different explants, observed highly heterogeneous responses IFNα or poly-I:C (a TLR3 ligand) when they were applied individually. contrast, combination uniformly enhanced CXCL10 CCL5 all lesions. Moreover, these effects could be optimized by further addition COX inhibitors. Applying triple also suppressed CCL22/MDC, associated regulatory (T(reg)). The T(eff)-enhancing treatment occurred selectively tissues, compared tissues derived from margins. These relied on increased propensity tumor-associated (mostly fibroblasts infiltrating inflammatory cells) hyperactivate NF-κB produce response treatment, resulting an ability treated attract T(reg) cells. Together, our findings suggest exploiting hyperactivation microenvironment enhance entry into colon tumors.