期刊
CANCER IMMUNOLOGY IMMUNOTHERAPY
卷 58, 期 8, 页码 1219-1228出版社
SPRINGER
DOI: 10.1007/s00262-008-0628-9
关键词
Tumor immunity; Regulatory CD4(+) T cells; Chemotherapy; Mesothelioma; Gemcitabine; Cyclophosphamide
资金
- National Health and Medical Research Council of Australia
Tumor cell death potentially engages with the immune system. However, the efficacy of anti-tumor chemotherapy may be limited by tumor-driven immunosuppression, e.g., through CD25(+) regulatory T cells. We addressed this question in a mouse model of mesothelioma by depleting or reconstituting CD25(+) regulatory T cells in combination with two different chemotherapeutic drugs. We found that the efficacy of cyclophosphamide to eradicate established tumors, which has been linked to regulatory T cell depletion, was negated by adoptive transfer of CD25(+) regulatory T cells. Analysis of post-chemotherapy regulatory T cell populations revealed that cyclophosphamide depleted cycling (Ki-67(hi)) T cells, including foxp3(+) regulatory CD4(+) T cells. Ki-67(hi) CD4(+) T cells expressed increased levels of two markers, TNFR2 and ICOS, that have been associated with a maximally suppressive phenotype according to recently published studies. This suggest that cyclophosphamide depletes a population of maximally suppressive regulatory T cells, which may explain its superior anti-tumor efficacy in our model. Our data suggest that regulatory T cell depletion could be used to improve the efficacy of anti-cancer chemotherapy regimens. Indeed, we observed that the drug gemcitabine, which does not deplete cycling regulatory T cells, eradicates established tumors in mice only when CD25(+) CD4(+) T cells are concurrently depleted. Cyclophosphamide could be used to achieve regulatory T cell depletion in combination with chemotherapy.
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