YAP Is Essential for Treg-Mediated Suppression of Antitumor Immunity
Abstract
Regulatory T cells (Treg) are critical for maintaining self-tolerance and immune homeostasis, but their suppressive function can impede effective antitumor immune responses. FOXP3 is a transcription factor expressed in Tregs that is required for their function. However, the pathways and microenvironmental cues governing FOXP3 expression and Treg function are not completely understood. Herein, we report that YAP, a coactivator of the Hippo pathway, is highly expressed in Tregs and bolsters FOXP3 expression and Treg function in vitro and in vivo. This potentiation stemmed from YAP-dependent upregulation of activin signaling, which amplifies TGFβ/SMAD activation in Tregs. YAP deficiency resulted in dysfunctional Tregs unable to suppress antitumor immunity or promote tumor growth in mice. Chemical YAP antagonism and knockout or blockade of the YAP-regulated activin receptor similarly improved antitumor immunity. Thus, we identify YAP as an unexpected amplifier of a Treg-reinforcing pathway with significant potential as an anticancer immunotherapeutic target.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Aug 01, 2018
- Source ID
- 10.1158/2159-8290.cd-17-1124
Entities
People
- Andriana Lebid
- Anjali Ramaswamy
- Benjamin V. Park
- Cui-ping Yang
- Drew M Pardoll
- Duojia Pan
- Fan Pan
- Huabin Li
- Jinhui Tao
- Joseph Barbi
- Ling Lu
- Nailing Zhang
- Paolo Vignali
- Ping Wei
- Qian Chen
- Xingmei Wu
- Xuehong Zhang
- Xuhao Ni
- Ying Zheng
- Zhiguang Li
Organizations
- Dalian Medical University
- First Affiliated Hospital of Xinjiang Medical University
- Fudan University
- Johns Hopkins School of Medicine
- Melanoma Research Alliance
- Melanoma Research Foundation
- Nanjing Medical University
- National Cancer Institute
- National Institutes of Health
- National Natural Science Foundation of China
- Roswell Park Comprehensive Cancer Center
- United States Department of Defense