論文 - 詳細
| RRC ID | 58764 |
|---|---|
| 著者 | Yahiro K, Matsumoto Y, Yamada H, Endo M, Setsu N, Fujiwara T, Nakagawa M, Kimura A, Shimada E, Okada S, Oda Y, Nakashima Y. |
| タイトル | Activation of TLR4 signaling inhibits progression of osteosarcoma by stimulating CD8-positive cytotoxic lymphocytes. |
| ジャーナル | Cancer Immunol Immunother |
| Abstract |
BACKGROUND:Osteosarcoma (OS) is the most common malignant bone tumor and the prognosis of advanced cases is still poor. Recently, there have been several reports suggesting the relationship between innate immunity and OS, but the detailed mechanism is unknown. We demonstrate the relationship between OS and Toll-like receptor 4 (TLR4) which is one of the most important factors in innate immunity. METHODS:We established a syngenic mouse tumor model using C3H/HeN, C3H/HeJ mouse and a highly metastatic OS cell line, LM8. TLR4 activation with lipopolysaccharide (LPS) was performed on both mice and its influence on the progression of OS was evaluated. We also performed CD8 + cells depletion to examine the influence on TLR4 activation effects. RESULTS:Tumor volume of C3H/HeN mice was significantly smaller and overall survival of C3H/HeN mice was significantly longer than C3H/HeJ mice. We found more CD8+ cells infiltrating in lung metastases of C3H/HeN mice and depletion of CD8+ cells canceled the antitumor effects of LPS. CONCLUSION:TLR4 activation by LPS increased CD8+ cells infiltrating into lung metastases and suppressed OS progression in the mouse model. TLR4 activation may suppress the progression of OS via stimulating CD8+ cells and can be expected as a novel treatment for OS. |
| 巻・号 | 69(5) |
| ページ | 745-758 |
| 公開日 | 2020-5-1 |
| DOI | 10.1007/s00262-020-02508-9 |
| PII | 10.1007/s00262-020-02508-9 |
| PMID | 32047957 |
| MeSH | Adjuvants, Immunologic / administration & dosage Adolescent Animals Antineoplastic Combined Chemotherapy Protocols / therapeutic use Bone Neoplasms / immunology* Bone Neoplasms / mortality Bone Neoplasms / pathology Bone Neoplasms / therapy Cell Line, Tumor / transplantation Chemotherapy, Adjuvant Child Child, Preschool Disease Models, Animal Disease Progression Female Humans Kaplan-Meier Estimate Lipid A / administration & dosage Lipid A / analogs & derivatives Lipopolysaccharides / administration & dosage Lung Neoplasms / immunology* Lung Neoplasms / mortality Lung Neoplasms / secondary Lung Neoplasms / therapy Lymphocyte Depletion Male Mice Middle Aged Osteosarcoma / immunology* Osteosarcoma / mortality Osteosarcoma / secondary Osteosarcoma / therapy Prognosis Progression-Free Survival Signal Transduction / drug effects Signal Transduction / immunology T-Lymphocytes, Cytotoxic / immunology* T-Lymphocytes, Cytotoxic / metabolism Toll-Like Receptor 4 / agonists Toll-Like Receptor 4 / immunology Toll-Like Receptor 4 / metabolism* Tumor Burden / immunology Young Adult |
| IF | 5.442 |
| 引用数 | 0 |
| リソース情報 | |
| ヒト・動物細胞 | LM8(RCB1450) |