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 Treg heterogeneity suggested increased terminal differentiation and stabilization of an effector phenotype over time. In particular, effector Tregs had enhanced expression of the interleukin 33 receptor ST2. Treg-specific deletion of ST2 reduced effector Tregs, increased infiltration of CD8+ T cells into tumors, and decreased tumor burden. Our study shows that ST2 plays a critical role in Treg-mediated immunosuppression in cancer, highlighting new potential paths for therapeutic intervention.

Download data

• Downloaded 1,884 times
• Download rankings, all-time:
  • Site-wide: 4,291 out of 94,912
  • In cancer biology: 97 out of 3,367
• Year to date:
  • Site-wide: 10,718 out of 94,912
• Since beginning of last month:
  • Site-wide: 15,034 out of 94,912

Altmetric data

Downloads over time

Distribution of downloads per paper, site-wide