On this perspective, RNASET2 was shown to apparently act in vivo as an alarmin-like molecule [25,47], leading the authors to speculate that, under early cancer cell-induced stressful condition experienced by the TME (such as hypoxia or nutrient starvation), the resulting increase in RNASET2 expression and secretion by cancer cells triggers a host defense response involving the recruitment and functional activation of M1 macrophages endowed with antitumoral activity. The gene discussed is RNASET2; the disease is cancer.