title: Tumor-infiltrating CD39+γδTregs are novel immunosuppressive T cells in human colorectal cancer.
abstract: Tumor microenvironment (TME) promotes immune suppression through recruiting and expanding suppressive immune cells such as regulatory T cells (Tregs) to facilitate cancer progression. In this study, we identify a novel CD39+γδTreg in human colorectal cancer (CRC). CD39+γδTregs are the predominant regulatory T cells and have more potent immunosuppressive activity than CD4+or CD8+Tregs via the adenosine-mediated pathway but independent of TGF-β or IL-10. They also secrete cytokines including IL-17A and GM-CSF, which may chemoattract myeloid-derived suppressive cells (MDSCs), thus establishing an immunosuppressive network. We further demonstrate that tumor-derived TGF-β1 induces CD39+γδT cells from paired normal colon tissues to produce more adenosine and become potent immunosuppressive T cells. Moreover, CD39+γδTreg infiltration is positively correlated with TNM stage and other unfavorable clinicopathological features, implicating that CD39+γδTregs are one of the key players in establishment of immunosuppressive TME in human CRC that may be critical for tumor immunotherapy.
authors.affiliation: Cancer Institute, Key Laboratory of Cancer Prevention & Intervention, National Ministry of Education, Provincial Key Laboratory of Molecular Biology in Medical Sciences, The Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University, Hangzhou, China; Department of Surgical Oncology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Guoming
authors.initials: G
authors.lastname: Hu
authors.affiliation: Cancer Institute, Key Laboratory of Cancer Prevention & Intervention, National Ministry of Education, Provincial Key Laboratory of Molecular Biology in Medical Sciences, The Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University, Hangzhou, China; Department of Thoracic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Pin
authors.initials: P
authors.lastname: Wu
authors.affiliation: Cancer Institute, Key Laboratory of Cancer Prevention & Intervention, National Ministry of Education, Provincial Key Laboratory of Molecular Biology in Medical Sciences, The Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University, Hangzhou, China; Department of Surgical Oncology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Pu
authors.initials: P
authors.lastname: Cheng
authors.affiliation: Department of Gynecology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University , Hangzhou, China.
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Cancer Institute, Key Laboratory of Cancer Prevention & Intervention, National Ministry of Education, Provincial Key Laboratory of Molecular Biology in Medical Sciences, The Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University, Hangzhou, China; Department of Surgical Oncology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Surgical Oncology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University , Hangzhou, China.
authors.forename: Xiuyan
authors.initials: X
authors.lastname: Yu
authors.affiliation: Department of Surgical Oncology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University , Hangzhou, China.
authors.forename: Xuan
authors.initials: X
authors.lastname: Shao
authors.affiliation: Department of Radiation Oncology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University , Hangzhou, China.
authors.forename: Dang
authors.initials: D
authors.lastname: Wu
authors.affiliation: Department of Gastroenterology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University , Hangzhou, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Ye
authors.affiliation: Cancer Institute, Key Laboratory of Cancer Prevention & Intervention, National Ministry of Education, Provincial Key Laboratory of Molecular Biology in Medical Sciences, The Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University , Hangzhou, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Zhang
authors.affiliation: Department of Surgical Oncology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University , Hangzhou, China.
authors.forename: Xiaochen
authors.initials: X
authors.lastname: Wang
authors.affiliation: Cancer Institute, Key Laboratory of Cancer Prevention & Intervention, National Ministry of Education, Provincial Key Laboratory of Molecular Biology in Medical Sciences, The Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University, Hangzhou, China; Department of Surgical Oncology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Fuming
authors.initials: F
authors.lastname: Qiu
authors.affiliation: Department of Medicine and Department of Microbiology and Immunology, James Graham Brown Cancer Center, University of Louisville , Louisville, KY, USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Yan
authors.affiliation: Cancer Institute, Key Laboratory of Cancer Prevention & Intervention, National Ministry of Education, Provincial Key Laboratory of Molecular Biology in Medical Sciences, The Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University, Hangzhou, China; Department of Surgical Oncology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Huang
keywords: Adenosine; CD39+ γδTregs; human CRC; tumor-derived TGF-β1