0 40

Cited 0 times in

Tumor-Infiltrating Regulatory T-cell Accumulation in the Tumor Microenvironment Is Mediated by IL33/ST2 Signaling

 Jimin Son  ;  Jae-Won Cho  ;  Hyo Jin Park  ;  Jihyun Moon  ;  Seyeon Park  ;  Hoyoung Lee  ;  Jeewon Lee  ;  Gamin Kim  ;  Su-Myeong Park  ;  Sergio A Lira  ;  Andrew N Mckenzie  ;  Hye Young Kim  ;  Cheol Yong Choi  ;  Yong Taik Lim  ;  Seong Yong Park  ;  Hye Ryun Kim  ;  Su-Hyung Park  ;  Eui-Cheol Shin  ;  Insuk Lee  ;  Sang-Jun Ha 
 CANCER IMMUNOLOGY RESEARCH, Vol.8(11) : 1393-1406, 2020-11 
Journal Title
Issue Date
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 tumor models, 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 proliferation-related genes, immune suppression-related genes, and cytokine/chemokine receptor genes were upregulated in tumor-infiltrating Tregs compared with tumor-infiltrating CD4+Foxp3- 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.
Full Text
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Thoracic and Cardiovascular Surgery (흉부외과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Hye Ryun(김혜련) ORCID logo https://orcid.org/0000-0002-1842-9070
Park, Seong Yong(박성용) ORCID logo https://orcid.org/0000-0002-5180-3853
사서에게 알리기


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.