Overview

• Macrophages ingest dying cancer cells and respond by producing inflammatory cytokines such as Upd3, triggering growth signals in surviving tumor cells.
• The cytokine Upd3, analogous to human interleukin-6, activates JAK and STAT proteins in remaining cancer cells, which in turn generate their own Upd3 to sustain a growth-promoting feedback loop.
• Genetic disruption of macrophage phagocytosis or targeted suppression of Upd3 production in fruit fly models led to a marked reduction in tumor expansion.
• The evolutionary conservation of this mechanism between fruit flies and humans suggests that similar macrophage–cancer cell interactions may drive aggressive tumor growth in human cancers.
• These findings challenge conventional immunotherapy approaches and identify the macrophage-driven cytokine feedback loop as a promising target for new cancer treatments.