title: Ex vivoexpanded human circulating Vδ1 γδT cells exhibit favorable therapeutic potential for colon cancer.
abstract: Gamma delta T (γδT) cells are innate-like lymphocytes with strong, MHC-unrestricted cytotoxicity against cancer cells and show a promising prospect in adoptive cellular immunotherapy for various malignancies. However, the clinical outcome of commonly used Vγ9Vδ2 γδT (Vδ2 T) cells in adoptive immunotherapy for most solid tumors is limited. Here, we demonstrate that freshly isolated Vδ1 γδT (Vδ1 T) cells from human peripheral blood (PB) exhibit more potent cytotoxicity against adherent and sphere-forming human colon cancer cells than Vδ2 T cellsin vitro. We also develop an optimized protocol to preferentially expand Vδ1 T cells isolated from PB of both healthy donors and colon cancer patients byin vitroshort-term culture with phytohemagglutinin (PHA) and interleukin-7 (IL-7). Expanded Vδ1 T cells highly expressed cytotoxicity-related molecules, chemokine receptors and cytokines with enhanced cytolytic effect against adherent and sphere-forming colon cancer cells in a cell-to-cell contact dependent manner. In addition, PHA and IL-7 expanded Vδ1 T cells showed proliferation and survival advantage partly through an IL-2 signaling pathway. Furthermore,ex vivoexpanded Vδ1 T cells also restrained the tumor growth and prolonged the tumor-burdened survival of human colon carcinoma xenografted mice. Our findings suggest that human PB Vδ1 T cells expanded by PHA and IL-7 are a promising candidate for anticancer adoptive immunotherapy for human solid tumors such as colon cancer.
authors.affiliation: Cancer Institute (Key Laboratory of Cancer Prevention & Intervention; National Ministry of Education; Provincial Key Laboratory of Molecular Biology in Medical Sciences), Second Affiliated Hospital; Zhejiang University School of Medicine ; Hangzhou, China ; Department of Oncology; Second Affiliated Hospital; Zhejiang University School of Medicine; Zhejiang University , Hangzhou, China.
authors.forename: Dang
authors.initials: D
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), Second Affiliated Hospital; Zhejiang University School of Medicine ; Hangzhou, China ; Department of Oncology; Second Affiliated Hospital; Zhejiang University School of Medicine; Zhejiang University , Hangzhou, China ; Department of Thoracic Surgery; Second Affiliated Hospital; Zhejiang University School of Medicine; Zhejiang University , Hangzhou, China.
authors.forename: Pin
authors.initials: P
authors.lastname: Wu
authors.affiliation: Department of Clinical Laboratory; Second Affiliated Hospital; Zhejiang University School of Medicine; Zhejiang University , Hangzhou, China.
authors.forename: Xianguo
authors.initials: X
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), Second Affiliated Hospital; Zhejiang University School of Medicine ; Hangzhou, China ; Department of Gastroenterology; 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), Second Affiliated Hospital; Zhejiang University School of Medicine ; Hangzhou, China ; Department of Oncology; Second Affiliated Hospital; Zhejiang University School of Medicine; Zhejiang University , Hangzhou, China.
authors.forename: Zhen
authors.initials: Z
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), Second Affiliated Hospital; Zhejiang University School of Medicine ; Hangzhou, China ; Department of Oncology; Second Affiliated Hospital; Zhejiang University School of Medicine; Zhejiang University , Hangzhou, China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Zhao
authors.affiliation: Cancer Institute (Key Laboratory of Cancer Prevention & Intervention; National Ministry of Education; Provincial Key Laboratory of Molecular Biology in Medical Sciences), Second Affiliated Hospital; Zhejiang University School of Medicine ; Hangzhou, China ; Department of Oncology; Second Affiliated Hospital; Zhejiang University School of Medicine; Zhejiang University , Hangzhou, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Ni
authors.affiliation: Cancer Institute (Key Laboratory of Cancer Prevention & Intervention; National Ministry of Education; Provincial Key Laboratory of Molecular Biology in Medical Sciences), Second Affiliated Hospital; Zhejiang University School of Medicine ; Hangzhou, China ; Department of Oncology; Second Affiliated Hospital; Zhejiang University School of Medicine; Zhejiang University , Hangzhou, China.
authors.forename: Guoming
authors.initials: G
authors.lastname: Hu
authors.affiliation: Department of Pathology; Second Affiliated Hospital; Zhejiang University School of Medicine; Zhejiang University ; Hangzhou, China.
authors.forename: Jinghong
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of Gastroenterology; Second Affiliated Hospital; Zhejiang University School of Medicine; Zhejiang University , Hangzhou, China.
authors.forename: Yuehua
authors.initials: Y
authors.lastname: Han
authors.affiliation: Department of Radiation Oncology; Second Affiliated Hospital; Zhejiang University School of Medicine; Zhejiang University , Hangzhou, China.
authors.forename: Ting
authors.initials: T
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), Second Affiliated Hospital; Zhejiang University School of Medicine ; Hangzhou, China ; Department of Oncology; 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), Second Affiliated Hospital; Zhejiang University School of Medicine ; Hangzhou, China ; Department of Oncology; Second Affiliated Hospital; Zhejiang University School of Medicine; Zhejiang University , Hangzhou, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Huang
keywords: Antigens, Ags; CCSCs, colon cancer stem cells; FACS, fluorescence activated cell sorting; FCM, flow cytometry; γδT cells, gamma delta T cells; IL-7, interleukin-7; MACS, magnetic activated cell sorting; PB, peripheral blood; PHA, phytohemagglutinin; PBMCs, peripheral blood mononuclear cells; Vδ2 T cells, Vγ9Vδ2 γδT cells; Vδ1 T cells, Vδ1 γδT cells; Zol, Zoledronate.; adoptive cellular immunotherapy; cytotoxicity; human PB Vδ1 T cells; human PB Vδ2 T cells; human colon cancer