Abstract
Liver fibrosis plays a crucial role in promoting tumor immune escape and tumor aggressiveness for liver cancer. However, an interesting phenomenon is that the tumor size of liver cancer patients with liver fibrosis is smaller than that of patients without liver fibrosis. In this study, 16 SD rats were used to establish orthotopic liver tumor transplantation models with Walker-256 cell lines, respectively on the fibrotic liver (n = 8, LF group) and normal liver (n = 8, control group). MRI (magnetic resonance imaging) was used to monitor the size of the tumors. All rats were executed at the third week after modeling, and the immunohistochemical staining was used to reflect the changes in the tumor microenvironment. The results showed that, compared to the control group, the PD-L1 (programmed cell death protein receptor-L1) expression was higher, and the neutrophil infiltration increased while the effector (CD8+) T cell infiltration decreased in the LF group. Additionally, the expression of MMP-9 (matrix metalloproteinase-9) of tumor tissue in the LF group increased. Three weeks after modeling, the size of tumors in the LF group was significantly smaller than that in the control group (382.47 ± 195.06 mm3 vs. 1736.21 ± 657.25 mm3, P < 0.001). Taken together, we concluded that liver fibrosis facilitated tumor immunity escape but limited the expansion of tumor size.
Highlights
Liver fibrosis plays a crucial role in promoting tumor immune escape and tumor aggressiveness for liver cancer
We deemed that the rats in the LF group suffered liver fibrosis from TAA injection was stopped until they were sacrificed, while the liver anatomy of the control group showed no apparent abnormalities
Much research has focused on the impact of liver fibrosis on the tumor m icroenvironment[24,27,28,29], but few studies focused on the effect of liver fibrosis on tumor size
Summary
Liver fibrosis plays a crucial role in promoting tumor immune escape and tumor aggressiveness for liver cancer. An interesting phenomenon is that the tumor size of liver cancer patients with liver fibrosis is smaller than that of patients without liver fibrosis. 16 SD rats were used to establish orthotopic liver tumor transplantation models with Walker-256 cell lines, respectively on the fibrotic liver (n = 8, LF group) and normal liver (n = 8, control group). The size of tumors in the LF group was significantly smaller than that in the control group (382.47 ± 195.06 m m3 vs 1736.21 ± 657.25 m m3, P < 0.001). The physical tension produced by collagen deposition which came from MFs may restrict the growth space of the tumor[13] Despite these theories, there is no literature to describe the relationship between tumor size and liver fibrosis. We established a rat orthotopic transplantation model with a liver fibrosis background, verified whether liver fibrosis causes tumor immunosuppression, and further explored the effect of liver fibrosis on tumor growth
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