A pivotal role for CC chemokine receptor 5 in T-cell migration to tumor sites induced by interleukin 12 treatment in tumor-bearing mice
| Autor: | Yasuhiro, Uekusa, Wen-Gong, Yu, Takao, Mukai, Ping, Gao, Nobuya, Yamaguchi, Masako, Murai, Kouji, Matsushima, Satoshi, Obika, Takeshi, Imanishi, Yuji, Higashibata, Shintaro, Nomura, Yukihiko, Kitamura, Hiromi, Fujiwara, Toshiyuki, Hamaoka |
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| Rok vydání: | 2002 |
| Předmět: |
Male
Mice Inbred BALB C Mice Inbred C3H Receptors CCR5 Fibrosarcoma T-Lymphocytes Neoplasms Experimental Macrophage Inflammatory Proteins Amides Interleukin-12 Up-Regulation Mice Inbred C57BL Quaternary Ammonium Compounds Mice Lymphocytes Tumor-Infiltrating Cell Movement CCR5 Receptor Antagonists Animals Humans Female RNA Messenger Chemokine CCL4 Spleen Chemokine CCL3 |
| Zdroj: | Cancer research. 62(13) |
| ISSN: | 0008-5472 |
| Popis: | Interleukin (IL) 12 treatment in the CSA1M and OV-HM, but not in Meth A tumor models,induces tumor regression that is associated with T-cell migration to tumor sites.Here, we investigated the role of the CC chemokine receptor (CCR)5 in T-cell migration induced after IL-12 treatment. In the two IL-12-responsive tumor models (CSA1M and OV-HM), IL-12 treatment up-regulated the mRNA expression of CCR5 in splenic T cells as well as ligands for CCR5, such as macrophage inflammatory protein (MIP) 1alpha and MIP-1beta in tumor masses. In contrast, the expression of CCR5 in spleens and MIP-1alpha/MIP-1beta in tumor masses was marginally induced before and even after IL-12 treatment in the Meth A model in which T-cell migration is not observed. T cells infiltrating tumor masses in the former two IL-12-responsive models expressed CCR5. Administration of a synthetic CCR5 antagonist TAK-779 to tumor-bearing mice during IL-12 immunotherapy prevented T-cell migration and tumor regression. Furthermore, anti-CCR5 antibody was found to inhibit T-cell migration in the lymphoid cell migration assay. Namely, although splenic T cells prepared from IL-12-treated CSA1M or OV-HM-bearing mice migrated into the corresponding tumor masses in recipient mice, the migration was inhibited when donor T cells were treated with anti-CCR5 antibody before the injection. These results indicate a critical role for CCR5 in the induction of T-cell migration to tumor sites after IL-12 treatment. |
| Databáze: | OpenAIRE |
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