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Single administration of low dose cyclophosphamide augments the antitumor effect of dendritic cell vaccine

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Abstract

Single administration of low dose cyclophosphamide (CTX) was previously reported to enhance the antitumor efficacy of immunotherapies. To investigate the possible mechanisms for this effect, we examined whether a single administration of low dose CTX could augment the immunogenicity of dendritic cell (DC) vaccines. Fifty milligrams per kilogram body weight dose of CTX was administrated intraperitoneally to mice after B16 melanoma or C26 colon carcinoma tumor models were established, DC vaccine generated from mouse bone marrow and pulsed with B16 or C26 tumor cells lysates were vaccinated 4 days later. CTX treatment potentiated the antitumor effects of the DC vaccine, and increased the proportion of IFN-γ secreting lymphocytes in spleens. Furthermore, a significantly reduced proportion of CD4+CD25+FoxP3+ regulatory T (Treg) cells was detected by flow cytometry in spleen lymphocytes from tumor-bearing mice treated with CTX. Thus, a single administration of low dose CTX could augment antitumor immune responses of DC vaccine by reducing the proportion of CD4+CD25+FoxP3+ Treg cells in tumor-bearing mice. Our results suggested a possible mechanism of CTX-induced immunopotentiation and provided a strategy of immunotherapy combining a low dose CTX with DC vaccine.

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Acknowledgments

This work is supported in part by grants from the National Natural Science Foundation of China (30600550), the Natural Science Foundation of Guangdong Province (04300289; 05001693), the Scientific Research Foundation of Sichuan Province (07KJT-09) and the International Collaboration Foundation of the Ministry of Science and Technology of China.

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Authors and Affiliations

  1. State Key Laboratory of Oncology in South China and Department of Biotherapy, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, 510060, Guangdong, People’s Republic of China

    Ji-Yan Liu, Xiao-Shi Zhang, Hong-Li Li, Yi Wang, Xia Cheng, Yong-Qiang Li, Jian-Chuan Xia & Yi-Xin Zeng

  2. State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan, People’s Republic of China

    Ji-Yan Liu, Yang Wu, Jin-Liang Yang & Yong-Qiu Mao

  3. Microbiology and Tumor Center, Karolinska Institute, Stockholm, Sweden

    Maria Masucci

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  1. Ji-Yan Liu
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Correspondence to Yi-Xin Zeng.

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J.-Y. Liu and Y. Wu contributed equally to this work.

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Liu, JY., Wu, Y., Zhang, XS. et al. Single administration of low dose cyclophosphamide augments the antitumor effect of dendritic cell vaccine. Cancer Immunol Immunother 56, 1597–1604 (2007). https://doi.org/10.1007/s00262-007-0305-4

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  • DOI: https://doi.org/10.1007/s00262-007-0305-4

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