期刊
CANCER BIOLOGY & THERAPY
卷 8, 期 1, 页码 66-72出版社
TAYLOR & FRANCIS INC
DOI: 10.4161/cbt.8.1.7131
关键词
adoptive cell transfer; regulatory T cell; 4T1; tumor infiltrating lymphocytes; Th1 type immune response; CD8(+)T cell; CD4(+)T cell
类别
资金
- LJ06011 [2007CB512401]
- China 863 [2006AA02Z403]
- China NSFC [30671952]
- Outstanding Medical Academic Leader [LJ06011]
Adoptive cell transfer (ACT) immunotherapy administered with prior host immunosuppression significantly improved the anti-tumor efficacy in a murine model. However, bulk transfer of lymphocytes containing suppressor lymphocyte subsets, including regulatory T cells to mice bearing late-stage tumors impaired this anti-tumor effect. In this study, we investigated the enhanced antitumor efficacy by adoptive transfer of Treg-depleted autologous tumor infiltrating lymphocytes in advanced murine breast cancer. We found that, compared to bulk cell transfer, Treg-depleted cell transfer enhanced the activation and proliferation of both CD4(+) and CD8(+) T cells. Most importantly, the immune response deviated towards the Th1 response reflected by increased IFN gamma and reduced IL-4 secretion in both CD4(+) and CD8+ T cells and an enhanced granzyme B release of CTL. Furthermore, the elicited Th1 response subsequently resulted in delayed tumor growth and prolonged mice survival as well as reduced lung metastasis in tumor-bearing nude mice. These results strongly indicated that Treg-depleted autologous cell transfer greatly enhanced Th1 type immune response, consequently leading to delayed tumor growth and reduced tumor burden. Therefore, ACT immunotherapy based on ex vivo selection of tumor-reactive lymphocytes resulted in enhanced anti-tumor immunity and provides important implications for further human studies.
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