Identification of RPL15 60S Ribosomal Protein as a Novel Topotecan Target Protein That Correlates with DAMP Secretion and Antitumor Immune Activation
| العنوان: | Identification of RPL15 60S Ribosomal Protein as a Novel Topotecan Target Protein That Correlates with DAMP Secretion and Antitumor Immune Activation |
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| المؤلفون: | Shunsuke Yamada, Yuichi Kitai, Takashi Tadokoro, Runa Takahashi, Haruka Shoji, Taiga Maemoto, Marie Ishiura, Ryuta Muromoto, Jun-ichi Kashiwakura, Ken J. Ishii, Katsumi Maenaka, Taro Kawai, Tadashi Matsuda |
| المصدر: | The Journal of Immunology. 209:171-179 |
| بيانات النشر: | The American Association of Immunologists, 2022. |
| سنة النشر: | 2022 |
| مصطلحات موضوعية: | Ribosomal Proteins, Mice, Neoplasms, Immunology, Animals, Immunology and Allergy, Topoisomerase I Inhibitors, Topotecan |
| الوصف: | Damage-associated molecular patterns (DAMPs) contribute to antitumor immunity during cancer chemotherapy. We previously demonstrated that topotecan (TPT), a topoisomerase I inhibitor, induces DAMP secretion from cancer cells, which activates STING-mediated antitumor immune responses. However, how TPT induces DAMP secretion in cancer cells is yet to be elucidated. Here, we identified RPL15, a 60S ribosomal protein, as a novel TPT target and showed that TPT inhibited preribosomal subunit formation via its binding to RPL15, resulting in the induction of DAMP-mediated antitumor immune activation independent of TOP1. TPT inhibits RPL15–RPL4 interactions and decreases RPL4 stability, which is recovered by CDK12 activity. RPL15 knockdown induced DAMP secretion and increased the CTL population but decreased the regulatory T cell population in a B16-F10 murine melanoma model, which sensitized B16-F10 tumors against PD-1 blockade. Our study identified a novel TPT target protein and showed that ribosomal stress is a trigger of DAMP secretion, which contributes to antitumor immunotherapy. |
| تدمد: | 1550-6606 0022-1767 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::22a67fbbcdf8cce9b6d15ea5b418d86bTest https://doi.org/10.4049/jimmunol.2100963Test |
| رقم الانضمام: | edsair.doi.dedup.....22a67fbbcdf8cce9b6d15ea5b418d86b |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15506606 00221767 |
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