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Article Abstract
Regulatory T cells (T cells) represent a primary barrier to the development of effective antitumor immunity. Here, we report that reprogramming T cells by shifting the expression of FOXP3 from its full-length isoform (FOXP3) to a short isoform with exon 2 skipped (FOXP3) promotes CD8 T cell-mediated antitumor immunity. mRNA expression in triple-negative breast cancer tissue positively correlated with overall patient survival. Mice expressing only the FOXP3 isoform were resistant to the development of multiple types of tumors. Tumor-infiltrating T cells expressing the FOXP3 isoform exhibited lower immunosuppressive activity and promoted CD8 T cell activation. In addition, we designed a morpholino oligo to induce FOXP3 exon 2 skipping, which similarly enhanced antitumor activity in mouse tumor models and the killing capacity of autologous tumor-infiltrating T cells against patient-derived tumor organoids. Our results suggest that promoting FOXP3 expression reprograms T cells to T helper-like cells, thereby enhancing antitumor immunity.
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| http://dx.doi.org/10.1126/sciimmunol.adr9933 | DOI Listing |
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