@article{oai:kanazawa-u.repo.nii.ac.jp:00027552, author = {中本, 安成 and 馬場, 智久 and 金子, 周一 and 向田, 直史 and Iida, Noriho and Nakamoto, Yasunari and Baba, Tomohisa and Kakinoki, Kaheita and Li, Ying-Yi and Wu, Yu and Matsushita, Kouji and Kaneko, Shuichi and Mukaida, Naofumi}, issue = {4}, journal = {Journal of Leukocyte Biology}, month = {Oct}, note = {The first step in the generation of tumor immunity is the migration of dendritic cells (DCs) to the apoptotic tumor, which is presumed to be mediated by various chemokines. To clarify the roles of chemokines, we induced apoptosis using suicide gene therapy and investigated the immune responses following tumor apoptosis. We injected mice with a murine hepatoma cell line, BNL 1ME A.7R.1 (BNL), transfected with HSV-thymidine kinase (tk) gene and then treated the animals with ganciclovir (GCV). GCV treatment induced massive tumor cell apoptosis accompanied with intratumoral DC infiltration. Tumor-infiltrating DCs expressed chemokine receptors CCR1 and CCR5, and T cells and macrophages expressed CCL3, a ligand for CCR1 and CCR5. Moreover, tumor apoptosis increased the numbers of DCs migrating into the draining lymph nodes and eventually generated a specific cytotoxic cell population against BNL cells. Although GCV completely eradicated HSV-tk-transfected BNL cells in CCR1-, CCR5-, or CCL3-deficient mice, intratumoral and intranodal DC infiltration and the subsequent cytotoxicity generation were attenuated in these mice. When parental cells were injected again after complete eradication of primary tumors by GCV treatment, the wild-type mice completely rejected the rechallenged cells, but the deficient mice exhibited impairment in rejection. Thus, we provide definitive evidence indicating that CCR1 and CCR5 and their ligand CCL3 play a crucial role in the regulation of intratumoral DC accumulation and the subsequent establishment of tumor immunity following induction of tumor apoptosis by suicide genes. © Society for Leukocyte Biology.全文公開200910, Embargo Period 12 months, 金沢大学がん研究所がん病態制御}, pages = {1001--1010}, title = {Tumor cell apoptosis induces tumor-specific immunity in a CC chemokine receptor 1- and 5-dependent manner in mice}, volume = {84}, year = {2008} }