The tumor microenvironment influences cancer progression and therapy outcome by
mechanisms not yet fully understood. In this issue, Bent et al. (2016) show how
chemotherapy causes endothelial senescence. Interestingly, senescent endothelial cells do
not mount a typical senescence-associated secretory phenotype but instead acutely secrete
IL-6, promoting chemoresistance. This study unveils a physiological switch involving
PI3K/AKT/mTOR signaling that restrains the senescence secretory responses to limit the
detrimental consequences of persistent inflammation.