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木犀草素通过加速 CD8+T 淋巴细胞浸润来发挥肝癌的抗肿瘤免疫作用。

Luteolin exerts anti-tumour immunity in hepatocellular carcinoma by accelerating CD8 T lymphocyte infiltration.

机构信息

Department of Pharmacy, Tianjin Medical University General Hospital, Tianjin, China.

Tianjin Key Laboratory of Digestive Diseases, Department of Gastroenterology and Hepatology, Tianjin Institute of Digestive Diseases, Tianjin Medical University General Hospital, Tianjin, China.

出版信息

J Cell Mol Med. 2024 Sep;28(17):e18535. doi: 10.1111/jcmm.18535.

Abstract

Luteolin, a commonly used traditional Chinese medicine, has been utilized for several decades in the treatment of hepatocellular carcinoma (HCC). Previous research has demonstrated its anti-tumour efficacy, but its underlying mechanism remains unclear. This study aimed to assess the therapeutic effects of luteolin in H22 tumour-bearing mice. luteolin effectively inhibited the growth of solid tumours in a well-established mouse model of HCC. High-throughput sequencing revealed that luteolin treatment could enhance T-cell activation, cell chemotaxis and cytokine production. In addition, luteolin helped sustain a high ratio of CD8 T lymphocytes in the spleen, peripheral blood and tumour tissues. The effects of luteolin on the phenotypic and functional changes in tumour-infiltrating CD8 T lymphocytes were also investigated. Luteolin restored the cytotoxicity of tumour-infiltrating CD8 T lymphocytes in H22 tumour-bearing mice. The CD8 T lymphocytes exhibited intensified phenotype activation and increased production of granzyme B, IFN-γ and TNF-α in serum. The combined administration of luteolin and the PD-1 inhibitor enhanced the anti-tumour effects in H22 tumour-bearing mice. Luteolin could exert an anti-tumour immune response by inducing CD8 T lymphocyte infiltration and enhance the anti-tumour effects of the PD-1 inhibitor on H22 tumour-bearing mice.

摘要

木樨草素是一种常用的中药,已被用于治疗肝细胞癌 (HCC) 数十年。先前的研究表明其具有抗肿瘤作用,但作用机制尚不清楚。本研究旨在评估木樨草素在 H22 荷瘤小鼠中的治疗效果。木樨草素可有效抑制 HCC 小鼠模型中实体瘤的生长。高通量测序显示,木樨草素治疗可增强 T 细胞激活、细胞趋化和细胞因子产生。此外,木樨草素有助于维持脾脏、外周血和肿瘤组织中 CD8 T 淋巴细胞的高比例。还研究了木樨草素对肿瘤浸润性 CD8 T 淋巴细胞表型和功能变化的影响。木樨草素恢复了荷瘤小鼠肿瘤浸润性 CD8 T 淋巴细胞的细胞毒性。CD8 T 淋巴细胞在血清中表现出增强的表型激活,并增加了颗粒酶 B、IFN-γ 和 TNF-α 的产生。木樨草素和 PD-1 抑制剂联合给药增强了荷瘤小鼠的抗肿瘤作用。木樨草素可通过诱导 CD8 T 淋巴细胞浸润发挥抗肿瘤免疫反应,并增强 PD-1 抑制剂对 H22 荷瘤小鼠的抗肿瘤作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6507/11392827/37bf2ffb457d/JCMM-28-e18535-g004.jpg

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