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- Title
Regulatory balance between the immune response of tumor antigen-specific T-cell receptor gene-transduced CD8<sup>+</sup> T cells and the suppressive effects of tolerogenic dendritic cells.
- Authors
Fujii, Shin-ichiro; Nishimura, Michael I.; Lotze, Michael T.
- Abstract
Tumor immune responses, including some immunotherapy strategies, can fail because of a number of reasons, such as poor tumor cell immunogenicity or local suppressive cytokine release by dendritic cells (DC) at tumor sites. The retroviral transfer of T-cell receptor (TCR) genes encoding tumor-specific receptors into T cells is a fascinating approach to bypass antigen-presenting cells and allow T cells to directly recognize antigen. It also allows the generation and expansion of potent antitumor cytotoxic T lymphocytes with defined cancer antigen specificities more readily than naive T cells. However, interleukin-10 (IL-10)-exposed dendritic cells (IL-10-DC) have been labeled tolerogenic because of the suppressive effects they have on T cell responses. Whether TCR gene-transduced effector CD8+ T cells can break through suppressive functions mediated by IL-10-DC is not known. In the current study, we demonstrate the role of IL-10 in modifying the function of DC that otherwise would activate potent TCR gene-transduced T cells against tumor antigens. TCR gene-transduced T cells maintained their cytolytic activity in the presence of DC exposed to low doses of IL-10 during maturation; however, they lost this activity in an antigen-specific manner when exposed to DC matured with high doses of IL-10. ( Cancer Sci 2005; 96: 897–902)
- Subjects
CELLS; LYMPHOCYTES; IMMUNE response; IMMUNOTHERAPY; T cells; DENDRITIC cells; ANTIGEN presenting cells; LYMPHOID tissue
- Publication
Cancer Science, 2005, Vol 96, Issue 12, p897
- ISSN
1347-9032
- Publication type
Article
- DOI
10.1111/j.1349-7006.2005.00124.x