A complex secretory program orchestrated by the inflammasome controls paracrine senescence Oncogene-induced senescence (OIS) is crucial for tumor suppression. Senescent cells implement a complex pro-inflammatory response termed the senescence-associated secretory phenotype (SASP). The SASP reinforces senescence, activates immune surveillance and paradoxically also has pro-tumourigenic properties. Here, we present evidence that the SASP can also induce "paracrine senescence" in normal cells both in culture and in human and mouse models of OIS in vivo. Coupling quantitative proteomics with small molecule screens, we identified multiple SASP components mediating paracrine senescence, including TGFβ family ligands, VEGF, CCL2 and CCL20. Amongst them, TGFβ ligands play a major role by regulating p15INK4b and p21CIP1. Expression of the SASP is controlled by inflammasome-mediated IL-1 signalling. The inflammasome and IL-1 signalling are activated in senescent cells and IL-1α expression can reproduce SASP activation, resulting in senescence. Our results demonstrate that the SASP can cause paracrine senescence and impact on tumor suppression and senescence in vivo. The SASP can exert opposing and contradictory effects. Initial studies focused on the pro-tumourigenic properties of the SASP but the SASP also mediates important tumour suppressive effects. Specific components of the SASP such as IGFBP-7, PAI-1, IL-6 and CXCR2-binding chemokines (such as IL-8 or GROα) can reinforce senescence. The SASP also contributes to the surveillance and elimination of senescent cells by the immune system. It is unclear whether pro-senescence effects can be exerted in non-cell-autonomous fashion (paracrine) in addition to cell-autonomous fashion (autocrine) and whether senescence can be transmitted to normal cells. Early experiments where 'young' and 'old' fibroblasts were mixed suggested that senescence was exclusively cell intrinsic although more recently a 'bystander senescence' response has been suggested. However, although some factors secreted by senescent cells, such as IL-6, reinforce senescence in an intracrine fashion, others like IGFBP-7 can display paracrine effects. In this investigation, we present unequivocal evidence supporting that senescence can be transmitted in a paracrine fashion, and provide insights into the pathways regulating and mediating paracrine senescence. Paracrine transmission of senescence by cells undergoing OIS To understand whether cells undergoing OIS can transmit senescence in a non-cell-autonomous manner, we established coA complex secretory program orchestrated by the inflammasome controls paracrine senescence Oncogene-induced senescence (OIS) is crucial for tumor suppression. Senescent cells implement a complex pro-inflammatory response termed the senescence-associated secretory phenotype (SASP). The SASP reinforces senescence, activates immune surveillance and paradoxically also has pro-tumourigenic properties. Here, we present evidence that the SASP can also induce "paracrine senescence" in normal cells both in culture and in human and mouse models of OIS in vivo. Coupling quantitative proteomics with small molecule screens, we identified multiple SASP components mediating paracrine senescence, including TGFβ family ligands, VEGF, CCL2 and CCL20. Amongst them, TGFβ ligands play a major role by regulating p15INK4b and p21CIP1. Expression of the SASP is controlled by inflammasome-mediated IL-1 signalling. The inflammasome and IL-1 signalling are activated in senescent cells and IL-1α expression can reproduce SASP activation, resulting in senescence. Our results demonstrate that the SASP can cause paracrine senescence and impact on tumor suppression and senescence in vivo. The SASP can exert opposing and contradictory effects. Initial studies focused on the pro-tumourigenic properties of the SASP but the SASP also mediates important tumour suppressive effects. Specific components of the SASP such as IGFBP-7, PAI-1, IL-6 and CXCR2-binding chemokines (such as IL-8 or GROα) can reinforce senescence. The SASP also contributes to the surveillance and elimination of senescent cells by the immune system. It is unclear whether pro-senescence effects can be exerted in non-cell-autonomous fashion (paracrine) in addition to cell-autonomous fashion (autocrine) and whether senescence can be transmitted to normal cells. Early experiments where 'young' and 'old' fibroblasts were mixed suggested that senescence was exclusively cell intrinsic although more recently a 'bystander senescence' response has been suggested. However, although some factors secreted by senescent cells, such as IL-6, reinforce senescence in an intracrine fashion, others like IGFBP-7 can display paracrine effects. In this investigation, we present unequivocal evidence supporting that senescence can be transmitted in a paracrine fashion, and provide insights into the pathways regulating and mediating paracrine senescence. Paracrine transmission of senescence by cells undergoing OIS To understand whether cells undergoing OIS can transmit senescence in a non-cell-autonomous manner, we established co