title: Immunotherapy of tumors with human telomerase reverse transcriptase immortalized human umbilical vein endothelial cells.
abstract: Human umbilical endothelial cells (HUVECs) have been proven to be effective in tumor anti-angiogenesis but the mechanism remained to be further demonstrated. The restricted ability of HUVECs to proliferate in vitro also limits their application on a large scale. In the present study, we immortalized HUVECs with hTERT genes by lentiviral infection and explored the antitumor immunity of hTERT-expressing HUVECs (HUVEC-TERTs). Results showed that HUVEC-TERTs maintained high telomere activity and expressed CD31, VEGFR-II and integrin α5. Passage-30 HUVEC-TERTs were able to form vascular tubes in vitro without showing signs of senescence. In vivo HUVEC-TERTs elicited antitumor immunity in mouse LL2 and CT26 models protectively and therapeutically. Both humoral and cellular immunity participated in the tumor anti-angiogenesis as HUVEC-neutralizing sera antibodies and HUVEC-specific CTL were detected. The subsets of activated spleen T lymphocytes included both CD4(+) T cells and CD8(+) T cells. Moreover, MDSCs and Tregs were decreased while T lymphocytes were aggregated in the tumor microenvironment. Collectively, the present study is the first to confirm the antitumor immunity of hTERT-immortalized HUVECs. Both anti-angiogenesis and tumor microenvironmental regulation participated in the antitumor activity. Transducing hTERT genes might be a new strategy to allow HUVECs to be applied on a large scale in cancer immunotherapy.
authors.affiliation: Department of Gynecology and Obstetrics, West China Second Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China.
authors.forename: Xiyan
authors.initials: X
authors.lastname: Mu
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, Sichuan 610041, P.R. China.
authors.forename: Yaxiong
authors.initials: Y
authors.lastname: Sang
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, Sichuan 610041, P.R. China.
authors.forename: Chunju
authors.initials: C
authors.lastname: Fang
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, Sichuan 610041, P.R. China.
authors.forename: Bin
authors.initials: B
authors.lastname: Shao
authors.affiliation: Department of Gynecology and Obstetrics, West China Second Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China.
authors.forename: Lu
authors.initials: L
authors.lastname: Yang
authors.affiliation: Department of Gynecology and Obstetrics, West China Second Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China.
authors.forename: Kui
authors.initials: K
authors.lastname: Yao
authors.affiliation: Department of Gynecology and Obstetrics, West China Second Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China.
authors.forename: Xitong
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Department of Gynecology and Obstetrics, West China Second Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China.
authors.forename: Jinhai
authors.initials: J
authors.lastname: Gou
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, Sichuan 610041, P.R. China.
authors.forename: Yuquan
authors.initials: Y
authors.lastname: Wei
authors.affiliation: Department of Gynecology and Obstetrics, West China Second Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China.
authors.forename: Tao
authors.initials: T
authors.lastname: Yi
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, Sichuan 610041, P.R. China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Department of Gynecology and Obstetrics, West China Second Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China.
authors.forename: Xia
authors.initials: X
authors.lastname: Zhao
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000276:immunology; D045744:Cell Line, Tumor; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D007167:Immunotherapy; D051379:Mice; D009369:Neoplasms / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D009389:Neovascularization, Pathologic / Q000276:immunology* / Q000628:therapy; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D019098:Telomerase / Q000235:genetics / Q000276:immunology*; D016615:Telomere / Q000235:genetics
chemical_list: D019496:Cancer Vaccines; C509186:TERT protein, human; D019098:Telomerase