TX-1877, a bifunctional hypoxic cell radiosensitizer, enhances anticancer host response: Immune cell migration and nitric oxide production
| Autor: | Soko Kasai, Sharif Uddin Ahmed, Masato Okamoto, Akiko Sasai, Yoshihiro Uto, Tetsuya Oshikawa, Sachiko Furuichi, Tomoyuki Tano, Hitoshi Hori, Mitsunobu Sato, Hideko Nagasawa, Shin Kan |
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| Rok vydání: | 2005 |
| Předmět: |
CD4-Positive T-Lymphocytes
Cancer Research Radiosensitizer Chemokine Immunopotentiator CD8-Positive T-Lymphocytes Nitric Oxide Radiation Tolerance Mice Immune system Cell Movement Animals Humans Cytotoxic T cell Antigen-presenting cell biology Dendritic Cells Cell Hypoxia Disease Models Animal Oncology Nitroimidazoles Cancer cell Immunology Carcinoma Squamous Cell biology.protein Cancer research CD8 T-Lymphocytes Cytotoxic |
| Zdroj: | International Journal of Cancer. 116:571-578 |
| ISSN: | 1097-0215 0020-7136 |
| DOI: | 10.1002/ijc.21101 |
| Popis: | We investigated in the current study the effect of TX-1877, a bifunctional hypoxic cell radiosensitizer, in augmenting anticancer host response. In the syngeneic squamous cell carcinoma-bearing mouse model, a single administration of TX-1877 significantly inhibited the primary tumor growth as well as lung metastasis. TX-1877 administration resulted in a significant infiltration of immune cells, such as CD4+T, CD8+T cells, macrophages and dendritic cells (DCs), and an increased expression of chemokines for cytotoxic T lymphocytes (CTLs), helper T-cell 1 (Th1) cells, monocytes/macrophages and DCs, in tumor tissues. Nitric oxide (NO) production and the expression of inducible NO synthase (iNOS) and interferon-γ, a major Th1 cytokine that plays a major role in anticancer immunity, were also enhanced. Furthermore, neutralization of NO by N-monomethyl-L-arginine acetate resulted in a marked inhibition of the antitumor effect of TX-1877. In tumor-draining lymph nodes, MHC class I-restricted CD8+ memory CTLs specific for inoculated cancer cells were induced by TX-1877. In in vitro experiments, TX-1877 induced chemokines and iNOS/NO in several types of culture cells. These findings strongly suggested that TX-1877 induces migration of CD8+CTLs, CD4+Th1 cells, macrophage/monocytes and dendritic cells into the tumor site, and that this migration is mediated by chemokine induction. In addition, it was suggested that NO produced by several types of cells stimulated by TX-1877 in the tumor sites plays a major role in the anticancer effect of TX-1877. TX-1877 was thus shown to be an effective immunopotentiator as well as a hypoxic cell radiosensitizer. © 2005 Wiley-Liss, Inc. |
| Databáze: | OpenAIRE |
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