经导管动脉栓塞增强了原位肝癌大鼠模型中程序性细胞死亡配体 1 的表达并影响 CD8T 淋巴细胞的细胞毒性。

Transarterial Embolization Enhances Programmed Cell Death Ligand 1 Expression and Influences CD8T Lymphocytes Cytotoxicity in an Orthotopic Hepatocellular Carcinoma Rat Model.

机构信息

Department of Interventional Radiology, The First Affiliated Hospital of Soochow University, No. 899, Pinghai Road, Suzhou, 215006, China.

Department of Pathology, The First Affiliated Hospital of Soochow University, Suzhou, China.

出版信息

Cardiovasc Intervent Radiol. 2024 Oct;47(10):1372-1381. doi: 10.1007/s00270-024-03813-x. Epub 2024 Aug 5.

DOI:10.1007/s00270-024-03813-x

PMID:39103638

Abstract

PURPOSE

To investigate the influence of transarterial embolization (TAE) on programmed cell death-ligand 1(PD-L1) expression and CD8T tumour infiltrative lymphocyte cytotoxicity in the Sprague-Dawley (SD) rat model of hepatocellular carcinoma (HCC).

MATERIALS AND METHODS

An orthotopic HCC model was established in twenty SD rats treated with TAE (lipiodol, n = 10) or sham (normal saline, n = 10) using homologous N1S1 hepatoma cells. Rats were euthanized 1 week after embolization. Flow cytometry was used to assess the proportion of CD4T, CD8T and programmed cell death-1(PD-1) CD8T lymphocytes in the spleens and tumours. Distribution of CD8T, granzyme-BCD8T lymphocytes and PD-L1 cells was assessed by immunohistochemistry (IHC) or multiplex IHC. p value < 0.05 was considered statistically significant.

RESULTS

The CD4/CD8 ratio and PD-1CD8 T lymphocytes exhibited higher values in TAE-treated tumours compared to sham-treated tumours (p = 0.021 and p = 0.071, respectively). Conversely, the number of CD8T lymphocytes was decreased in TAE-treated tumours (p = 0.043), especially in the central region (p = 0.045). However, more CD8T lymphocytes were found infiltrating the marginal region than central region in TAE-treated tumours (p = 0.046). The proportion of granzyme-BCD8T lymphocytes and the PD-L1 positive areas was elevated in tumours that treated with TAE (p all < 0.05). There was a negative correlation between PD-L1 expression and the number of infiltration of CD8 T lymphocytes (p = 0.036).

CONCLUSIONS

Immune cells are distributed unevenly in the tumours after TAE. The intrinsic induction state of the tumour after embolization may be insufficient to elicit a maximal response to PD-1/PD-L1 inhibitors.

摘要

目的

研究经肝动脉栓塞术（TAE）对肝癌（HCC）Sprague-Dawley（SD）大鼠模型中程序性死亡配体 1（PD-L1）表达和 CD8+T 肿瘤浸润淋巴细胞细胞毒性的影响。

材料和方法

使用同源 N1S1 肝癌细胞，在 20 只 SD 大鼠中建立原位 HCC 模型，分别采用 TAE（碘油，n=10）或假手术（生理盐水，n=10）治疗。栓塞后 1 周处死大鼠。流式细胞术检测脾脏和肿瘤中 CD4+T、CD8+T 和程序性死亡-1（PD-1）+CD8+T 淋巴细胞的比例。免疫组化（IHC）或多重免疫组化检测 CD8+T、颗粒酶 B+CD8+T 淋巴细胞和 PD-L1 细胞的分布。p 值<0.05 为差异有统计学意义。

结果

与假手术组相比，TAE 治疗组肿瘤中的 CD4/CD8 比值和 PD-1+CD8+T 淋巴细胞比例更高（p=0.021 和 p=0.071）。相反，TAE 治疗组肿瘤中 CD8+T 淋巴细胞数量减少（p=0.043），尤其是在中央区域（p=0.045）。然而，在 TAE 治疗组肿瘤的边缘区域浸润的 CD8+T 淋巴细胞多于中央区域（p=0.046）。TAE 治疗组肿瘤中颗粒酶 B+CD8+T 淋巴细胞的比例和 PD-L1 阳性面积增加（p 均<0.05）。PD-L1 表达与 CD8+T 淋巴细胞浸润数量呈负相关（p=0.036）。