Our latest study reveals how colorectal cancer (CRC) tumors can directly shape the immune microenvironment by inducing a unique population of regulatory T (Treg) cells. Using a novel 3D organoid-T cell co-culture system, Sonia Aristin found that CRC tumor-derived organoids promote CD4+ T cell differentiation into a distinct, highly immunosuppressive Treg subset—without direct cell contact. These organoid-induced Tregs (TO-iTregs) have a unique transcriptional profile resembling tumor-infiltrating Tregs in CRC patients. Furthermore, high expression of TO-iTreg signature genes correlates with worse clinical outcomes in CRC. This model provides a new platform to explore immune regulation and develop strategies to disrupt tumor-induced immunosuppression.