Activated RAS/BRAF oncogenes induce cellular senescence as a tumor-suppressive 
barrier in early cancer development, at least in part, via an oncogene-evoked 
DNA damage response (DDR). In contrast, Myc activation-although producing a DDR 
as well-is known to primarily elicit an apoptotic countermeasure. Using the 
Emu-myc transgenic mouse lymphoma model, we show here in vivo that apoptotic 
lymphoma cells activate macrophages to secrete transforming growth factor beta 
(TGF-beta) as a critical non-cell-autonomous inducer of cellular senescence. 
Accordingly, neutralization of TGF-beta action, like genetic inactivation of the 
senescence-related histone methyltransferase Suv39h1, significantly accelerates 
Myc-driven tumor development via cancellation of cellular senescence. These 
findings, recapitulated in human aggressive B cell lymphomas, demonstrate that 
tumor-prompted stroma-derived signals may limit tumorigenesis by feedback 
senescence induction.