Polarization of M1 tumor associated macrophage promoted by the activation of TLR3 signal pathway.
OBJECTIVE
To investigate the correlation between activation of toll-like receptors 3 (TLR3) signaling pathway and tumor-associated macrophage and its effect on the tumor growth.


METHODS
The mice Lewis lung cancer cell lines 3LL and melanoma B16H10 were used to construct the subcutaneous transplantation tumor models and then they were treated with Poly-ICLC. The curative effect was observed and then the T cell and macrophage phenotypes infiltrated in local tumor were detected by flow cytometry. After the in vitro culture of mouse bone marrow-derived macrophage, the real-time PCR and western blot were applied to detect the expression of macrophage activation markers and the activation of intracellular signaling pathways.


RESULTS
The survival time of mice with brown tumor treated with Poly-ICLC significantly increased and the tumor growth was inhibited. The ratio of local tumor-infiltrated Treg decreased, while the ratio of CD8(+) T cell increased significantly. The macrophages surface CD206 expression was down-regulated while the expression of iNOS increased. The Poly-ICLC could promote the expression of M1 markers (IL-1β, TNF-α and iNOS) in bone marrow-derived macrophage and inhibited the expression of M2 molecules (Arg-1, YM-1 and CD206). The phosphorylation level of downstream p65, TBK1 and IRF3 increased significantly.


CONCLUSIONS
The Poly-ICLC can activate the TLR3 downstream signaling pathway to induce a M1 polarization of tumor associated macrophage, thereby inhibiting the tumor growth.
Department of Pediatric Surgery, Yongchuan Hospital of Chongqing Medical University, Chongqing 402160, China. Electronic address: zsfvaca@126.com.
Bo
B
Liu
Department of Pediatric Surgery, Yongchuan Hospital of Chongqing Medical University, Chongqing 402160, China.
Xia
X
Wang
Department of Pediatric Surgery, Yongchuan Hospital of Chongqing Medical University, Chongqing 402160, China.
Tai-Zhong
TZ
Chen
Department of Pediatric Surgery, Yongchuan Hospital of Chongqing Medical University, Chongqing 402160, China.
Guang-Liang
GL
Li
Department of Pediatric Surgery, Yongchuan Hospital of Chongqing Medical University, Chongqing 402160, China.
Chang-Chun
CC
Tan
Department of Pediatric Surgery, Yongchuan Hospital of Chongqing Medical University, Chongqing 402160, China.
Yong
Y
Chen
Department of Pediatric Surgery, Yongchuan Hospital of Chongqing Medical University, Chongqing 402160, China.
Shao-Qiang
SQ
Duan
M1; Poly-ICLC; TLR3; Tumor-associated macrophage