期刊
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
卷 108, 期 1, 页码 115-125出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.ijrobp.2019.09.041
关键词
-
资金
- National Research Foundation of Korea [2016R1D1A1B03936394]
- National R&D Program for Cancer Control, Ministry of Health & Welfare, Republic Korea [1720120]
- National Research Foundation of Korea [2016R1D1A1B03936394] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
Purpose: We investigated whether adoptive cell therapy with ex vivo-activated natural killer (NK) cells enhances the therapeutic efficacy of local tumor radiation therapy (RT) using a human triple-negative breast cancer xenograft model. Methods and Materials: NK cells from healthy donors were expanded ex vivo. MDA-MB-231/Luc-GFP cells were subcutaneously implanted into the thighs of NSG mice. The animals were divided into 4 experimental groups: control, RT, NK, and RT + NK. On day 17 after tumor implantation, tumors from the RT groups were irradiated. The ex vivo-expanded NK cells were intravenously administered twice, on days 17 and 19. Primary and secondary tumors were evaluated using long-term bioluminescence imaging, and histopathology was performed on resected tumor tissue specimens. Results: The luciferase signals of the primary tumors in the RT + NK group were significantly lower than those of comparably sized primary tumors in the RT group. The long-term migration and infiltration of NK cells into the primary tumor sites were significantly higher in RT NK than in NK mice. Moreover, lymphatic metastasis to the axillary lymph nodes and liver and lung metastases were highly suppressed in the RT + NK group, as demonstrated by BLI and p53 immunohistochemistry. The long-term survival of the RT + NK group was significantly higher than that of the RT or NK groups. Conclusions: Reduction in tumor burden by combining RT and systemic NK cell therapy improved the suppression of primary tumor growth, with efficient NK cell migration and penetration into the primary tumor site. Administered NK cells were maintained in the primary tissue for a significantly longer time in RT + NK group compared with NK group. Both lymphatic spread and distant metastasis to the lungs and liver were effectively suppressed by the combined therapy. (C) 2019 Elsevier Inc. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据