Lineage tracing and targeting of IL17RB + tuft cell-like human colorectal cancer stem cells

Significance Cancer stem cells, capable of self-renewing and giving rise to progeny cells in the tumor, have attracted attention as potential therapeutic targets. In this study, using genetically engineered mouse models, we showed that IL17RB, a tuft cell marker in the intestine, does not mark normal stem cells but marks tumor stem cells of mouse intestinal adenomas. Furthermore, using CRISPR-Cas9–mediated IL17RB-CreERT2 knockin human organoids, we showed that IL17RB marks human colorectal cancer stem cells by lineage tracing, and that long-term targeting of IL17RB + cells strongly suppressed the tumor growth in vivo. This study identifies IL17RB + cancer stem cells and preclinically validates them as a cancer therapeutic target.