SUMO2 Deletion Changes Chromatin Accessibility and Enhances Cytotoxic T Cell Activation and Tumor Infiltration [human_ATACseq]

Using antigen-specific T cell models, OT1 and Chimeric Antigen Receptor (CAR)-T cells, we found that Sumo2 KO CD8+ T cells had significantly higher tumor infiltration as revealed by flow cytometry, immuno-fluorescence (IF) staining, and single nuclei RNA-sequencing (snRNA-seq) and conferred greater tumor growth inhibition than wildtype (WT) control T cells. snRNA-seq also revealed Sumo2 KO CD8+ T cells increased the expression of Tumor Necrosis Factor-Related Apoptosis-inducing Ligand (TRAIL) and induced apoptosis genes in tumor cells and profound changes in all cell types in the TME.

These findings elucidate a novel mechanism regarding how post-translational modifications with SUMO can directly control CTL activation, tumor infiltration and cell-cell interactions in antitumor adaptive immunity. SUMO2 KO can also be a potential strategy to enhance adoptive T cell therapies of solid tumors by enhancing their activity and tumor infiltration.