Immunotherapy of tumors with human telomerase reverse transcriptase immortalized human umbilical vein endothelial cells

Mu,Xiyan; Sang,Yaxiong; Fang,Chunju; Shao,Bin; Yang,Lu; Yao,Kui; Zhao,Xitong; Gou,Jinhai; Wei,Yuquan; Yi,Tao; Wu,Yang; Zhao,Xia

doi:10.3892/ijo.2015.3175

Immunotherapy of tumors with human telomerase reverse transcriptase immortalized human umbilical vein endothelial cells

Authors:
- Xiyan Mu
- Yaxiong Sang
- Chunju Fang
- Bin Shao
- Lu Yang
- Kui Yao
- Xitong Zhao
- Jinhai Gou
- Yuquan Wei
- Tao Yi
- Yang Wu
- Xia Zhao
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Affiliations: Department of Gynecology and Obstetrics, West China Second Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China, 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
Published online on: September 21, 2015 https://doi.org/10.3892/ijo.2015.3175
Pages: 1901-1911

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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.

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