Open AccessRegulatory balance between the immune response of tumor antigen‐specific T‐cell receptor gene‐transduced CD8 + T cells and the suppressive effects of tolerogenic dendritic cells
Author(s) -
Fujii Shinichiro,
Nishimura Michael I.,
Lotze Michael T.
Publication year - 2005
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/j.1349-7006.2005.00124.x
Subject(s) - cytotoxic t cell , biology , antigen , antigen presenting cell , immune system , t cell , t cell receptor , cd8 , immunotherapy , interleukin 21 , il 2 receptor , interleukin 12 , immunology , microbiology and biotechnology , in vitro , biochemistry
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)