The evidence that many of the Notch target genes encoding for cytokines, i.e., IL-1β, IL-6, IL-8, CCL2, and CCL5 (31, 33, 173, 195), above reported in different tumor settings are negatively regulated by Notch during cancer cell senescence underlines that Notch signaling outcome is highly context dependent. The gene discussed is IL6; the disease is cancer.