Reprogramming intratumoral T_reg cells by morpholino-mediated splicing of FOXP3 for cancer immunotherapy

Editor’s summary

The master regulator of regulatory T (T_reg) cells, FOXP3, is present in humans as two major variants, including a shorter isoform lacking exon 2 (FOXP3^dE2). Li et al. found that mice expressing the FOXP3^dE2 isoform were resistant to the growth of multiple tumor types. Tumor-infiltrating T_reg cells from Foxp3^dE2 mice were less suppressive of CD8 T cell responses and produced higher levels of effector cytokines, including IFN-γ. A morpholino oligo that induced the skipping of FOXP3 exon 2 slowed growth of tumors in mice and organoids derived from patients with breast or colorectal cancer. These findings suggest that targeting FOXP3 isoform usage could be an approach to alleviate T_reg cell–mediated tumor immunosuppression. —Claire Olingy