Tumor-initiating cells establish an IL-33–TGF-β niche signaling loop to promote cancer progression

Deconstructing a perilous loop Cancer cells that give rise to solid tumors reside in a specialized microenvironment containing growth factors that support tumor growth and progression. The mechanisms by which tumor cells within this so-called “niche” attract and sustain these growth factors are poorly understood. Studying a mouse model of squamous cell carcinoma, Taniguchi et al. identified a signaling loop initiated by certain tumor cells within the niche that become more invasive on exposure to transforming growth factor β (TGF-β). They show that the tumor cells release the cytokine interleukin-33, which induces the differentiation of nearby myeloid cells into macrophages. These macrophages in turn release TGF-β, which feeds back to the tumor cells, promoting their malignant progression. Science this issue p. eaay1813