EdItOr’s caOrnEr EdItOrIaL

p53 is a central sensor of severe cellular insults, including genotoxic, oxidative and oncogenic stress. Depending on the con-text, p53 cell-autonomously orchestrates responses of temporary cell cycle arrest coupled to DNA repair or permanent senescence, or it induces apoptotic, autoph-agic and necrotic forms of cell death.1–3 However, little is known about the non-cell autonomous effects of p53. Recent findings from Lujambio et al. uncover a new paracrine oncosuppressor function of p53 in chronic liver damage, a cytokine-dependent process that promotes an anti-tumorigenic microenvironment (at least in part) by modulating immunosurveillance.4 Upon liver injury, stromal hepatic stel-late cells (HSC) become activated and drive the fibrotic scarring of the liver parenchyma. Chronic liver injury coupled to smoldering fibrosis can result in cir-rhosis, a main risk factor for hepatocellu-lar carcinoma (HCC). The same authors had previously shown that p53 mediates a senescence program in HSCs that limits fibrosis and maintains tissue homeostasis. Such a p53-dependent senescence program is executed in cooperation with NFκB and induces the so-called senescence-associ-ated secretory phenotype (SASP). The SASP is marked by the downregulation of extracellular matrix (ECM) proteins including collagen, by the upregulation of ECM-degrading enzymes and by produc-tion of immunomodulatory factors and inflammatory cytokines.5,6 The fibrosis-inhibitory effect of dam-age-activated p53 in HSCs was confirmed p53 further extends its reac