Regulatory T cells in the Tumor Microenvironment Display a Unique Chromatin Accessibility Profile (ATAC-Seq)

Regulatory T cells (Tregs) are a suppressive CD4+ T cell population that limit the anti-tumor immune response. In this study, we analyzed the chromatin accessibility of Tregs in the murine tumor microenvironment (TME) to identify tumor-specific accessible peaks and if these are altered over time in the tumor microenvironment, with or without anti-PD1 immunotherapy. We found that Tregs have a more distinct chromatin accessibility signature in the TME compared to Tregs in the periphery than within location over time in the models we accessed. This distinct tumor Treg chromatin accessibility profile highlights reduced accessibility at loci important for an CD4+ conventional T cell (CD4+ Foxp3—) effector phenotype and reinforcement of a suppressive phenotype. Analysis of chromatin accessibility in Tregs in B16 and MC38 tumor models indicated similar regulation independent of tumor type, indicating a tumor-derived Treg effector signature in the models we accessed. We also found that Tregs do not alter their transcriptome nor chromatin accessibility following immunotherapy. We conclude that chromatin accessibility in Tregs is altered in the TME, but is otherwise remarkably stable and appears unaltered by tumor type, over time, or following immunotherapy. Regulatory T cells from the murine B16 and MC38 tumor microenvironment were accessed for chromatin accesibility by bulk ATAC-sequencing.