چکیده (انگلیسی):

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-1b, TNF-a 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.