Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jiefang Avenue #1277, Wuhan, 430022, China.
Hubei Province Key Laboratory of Molecular Imaging, Wuhan, 430022, China.
Sci Rep. 2021 Nov 24;11(1):22846. doi: 10.1038/s41598-021-02155-9.
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 mm vs. 1736.21 ± 657.25 mm, P < 0.001). Taken together, we concluded that liver fibrosis facilitated tumor immunity escape but limited the expansion of tumor size.
肝纤维化在促进肝癌肿瘤免疫逃逸和侵袭性方面起着关键作用。然而，有一个有趣的现象是，伴有肝纤维化的肝癌患者的肿瘤大小比没有肝纤维化的患者小。在这项研究中，使用 16 只 SD 大鼠分别在纤维化肝脏（n=8，LF 组）和正常肝脏（n=8，对照组）上建立 Walker-256 细胞系的原位肝癌移植模型。使用 MRI（磁共振成像）监测肿瘤的大小。所有大鼠均在建模后第三周处死，并进行免疫组织化学染色以反映肿瘤微环境的变化。结果表明，与对照组相比，LF 组的 PD-L1（程序性死亡受体配体 1）表达更高，中性粒细胞浸润增加，而效应（CD8+）T 细胞浸润减少。此外，LF 组肿瘤组织中 MMP-9（基质金属蛋白酶-9）的表达增加。建模后 3 周，LF 组肿瘤的大小明显小于对照组（382.47±195.06 mm 对 1736.21±657.25 mm，P<0.001）。综上所述，我们得出结论，肝纤维化促进了肿瘤免疫逃逸，但限制了肿瘤大小的扩张。
