제목 | [논문] 하상준 교수님_Tumor-infiltrating regulatory T cell accumulation in the tumor microenvironment is mediated by IL33/ST2... | ||||
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작성자 | 비임파성 장기 면역 연구센터 | 등록일 | 2021-01-26 | 조회수 | 1111 |
Tumor-infiltrating regulatory T cell accumulation in the tumor microenvironment is mediated by IL33/ST2 signaling
Regulatory T cells (Treg) are enriched in the tumor microenvironment (TME) and suppress antitumor immunity; however, the molecular mechanism underlying the accumulation of Tregs in the TME is poorly understood. In various tumormodels, tumor-infiltrating Tregs were highly enriched in the TME and had significantly higher expression of immune checkpoint molecules. To characterize tumor-infiltrating Tregs, we performed bulk RNA sequencing (RNA-seq) and found that proliferationrelated genes, immune suppression–related genes, and cytokine/ chemokine receptor genes were upregulated in tumor-infiltrating Tregs compared with tumor-infiltrating CD4þFoxp3 conventional T cells or splenic Tregs from the same tumor-bearing mice. Single-cell RNA-seq and T-cell receptor sequencing also revealed active proliferation of tumor infiltrating Tregs by clonal expansion. One of these genes, ST2, an IL33 receptor, was identified as a potential factor driving Treg accumulation in the TME. Indeed, IL33-directed ST2 signaling induced the preferential proliferation of tumor-infiltrating Tregs and enhanced tumor progression, whereas genetic deletion of ST2 in Tregs limited their TME accumulation and delayed tumor growth. These data demonstrated the IL33/ST2 axis in Tregs as one of the critical pathways for the preferential accumulation of Tregs in the TME and suggests that the IL33/ST2 axis may be a potential therapeutic target for cancer immunotherapy. |