Improving the in vivo Persistence, Distribution and Function of Cytotoxic T Lymphocytes by Inhibiting the Tumor Immunosuppressive Microenvironment

作者：Weili Xu, Jianhui Cai, Shouhua Li, H Zhang, Jing‐Zhao Han, Ming Wen, Jiaxin Wen, Fei Gao · 发表于：Scandinavian Journal of Immunology · 年份：2013 · DOI：10.1111/sji.12065 · 被引用次数：8 · 研究领域：Immunotherapy and Immune Responses、CAR-T cell therapy research、Immune Cell Function and Interaction

Adoptive cell transfer immunotherapy of malignant tumors has the problem of symbiosis between effector cells and tumor cells, a short in vivo residence time, and a poor killing efficiency of effector cells. Thus, releasing effector cells from the cancer immunosuppressive microenvironment and improving their effective time and functional status in vivo would seem to be ideal strategies for facilitating immunotherapy. Low-dose cyclophosphamide administration can effectively break immunotolerance by inhibiting regulatory T cells. In the present study, in order to verify whether the persistence, distribution and function of effector cells can be improved by inhibiting immunosuppressive microenvironment, low-dose cyclophosphamide was previously intraperitoneally injected into melanoma-bearing C57BL/6 mice, thereafter, CFSE-labeled cytotoxic T lymphocytes were transfused intravenously, and their effective time, distributive pattern, and killing efficiency in different groups were observed by measuring the fluorescence intensity and cell cycle of cytotoxic T lymphocytes distributed in various organs, in comparison with tumor growth. We found down-regulating Tregs in vivo can simultaneously reduce the levels of interleukin-10 and transforming growth factor-β. Migration and distribution of cytotoxic T lymphocytes in vivo was found to vary with time. Inhibition of immunotolerance can significantly improve the persistence, distribution, and function of cytotoxic T lymphocytes. Correspon...