TY - JOUR
T1 - Activation of TLR4 signaling inhibits progression of osteosarcoma by stimulating CD8-positive cytotoxic lymphocytes
AU - Yahiro, Kenichiro
AU - Matsumoto, Yoshihiro
AU - Yamada, Hisakata
AU - Endo, Makoto
AU - Setsu, Nokitaka
AU - Fujiwara, Toshifumi
AU - Nakagawa, Makoto
AU - Kimura, Atsushi
AU - Shimada, Eijiro
AU - Okada, Seiji
AU - Oda, Yoshinao
AU - Nakashima, Yasuharu
N1 - Funding Information:
This work was supported by Grants-in-Aid for Young Scientists (18K16627, 19K16802), Grant-in-Aid for Scientific Research (18K09067) from the Japan Society for the Promotion of Science, a Grant from Japan Orthopedics and Traumatology Research Foundation Inc. (No. 332). Toshifumi Fujiwara was also recipient of Fukuoka Foundation for Sound Health Cancer Research Fund. Acknowledgements
Funding Information:
We thank Dr. Tetsuzo Tagawa from Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University for kindly providing clinical samples of the patients with OS.
Publisher Copyright:
© 2020, Springer-Verlag GmbH Germany, part of Springer Nature.
PY - 2020/5/1
Y1 - 2020/5/1
N2 - 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.
AB - 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.
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U2 - 10.1007/s00262-020-02508-9
DO - 10.1007/s00262-020-02508-9
M3 - Article
C2 - 32047957
AN - SCOPUS:85079462721
SN - 0340-7004
VL - 69
SP - 745
EP - 758
JO - Cancer Immunology, Immunotherapy
JF - Cancer Immunology, Immunotherapy
IS - 5
ER -
