Longitudinal Single Cell Profiling of Regulatory T Cells Identifies IL-33 as a Driver of Tumor Immunosuppression
88 Pages Posted: 19 Mar 2019 Sneak Peek Status: Review CompleteMore...
Regulatory T cells (Tregs) can impair anti-tumor immune responses and are associated with poor prognosis in multiple cancer types. Tregs in human tumors span diverse transcriptional states distinct from those of peripheral Tregs, but their contribution to tumor development remains unknown. Here, we used single cell RNA-Seq to longitudinally profile conventional CD4+ T cells (Tconv) and Tregs in a genetic mouse model of lung adenocarcinoma. Tissue-infiltrating and peripheral CD4+ T cells differed, highlighting divergent pathways of activation during tumorigenesis. Longitudinal shifts in Tregs heterogeneity suggested stabilization of a specialized effector phenotype over time that had enhanced expression of the interleukin 33 receptor ST2. Tregs-specific deletion of ST2 altered lung effector Tregs diversity, increased infiltration of CD8+ T cells into tumors, and decreased tumor burden. Our study shows that ST2 plays a critical role in Tregs-mediated immunosuppression in cancer, highlighting new potential paths for therapeutic intervention.
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