{"title":"木犀草素通过加速 CD8+ T 淋巴细胞浸润对肝细胞癌发挥抗肿瘤免疫作用","authors":"Shijiao Cai, Yidan Gou, Yanyan Chen, Xiaoran Hou, Jing Zhang, Chongwen Bi, Peng Gu, Miao Yang, Hanxu Zhang, Weilong Zhong, Hengjie Yuan","doi":"10.1111/jcmm.18535","DOIUrl":null,"url":null,"abstract":"<p>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<sup>+</sup> T lymphocytes in the spleen, peripheral blood and tumour tissues. The effects of luteolin on the phenotypic and functional changes in tumour-infiltrating CD8<sup>+</sup> T lymphocytes were also investigated. Luteolin restored the cytotoxicity of tumour-infiltrating CD8<sup>+</sup> T lymphocytes in H22 tumour-bearing mice. The CD8<sup>+</sup> 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<sup>+</sup> T lymphocyte infiltration and enhance the anti-tumour effects of the PD-1 inhibitor on H22 tumour-bearing mice.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":null,"pages":null},"PeriodicalIF":5.3000,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.18535","citationCount":"0","resultStr":"{\"title\":\"Luteolin exerts anti-tumour immunity in hepatocellular carcinoma by accelerating CD8+ T lymphocyte infiltration\",\"authors\":\"Shijiao Cai, Yidan Gou, Yanyan Chen, Xiaoran Hou, Jing Zhang, Chongwen Bi, Peng Gu, Miao Yang, Hanxu Zhang, Weilong Zhong, Hengjie Yuan\",\"doi\":\"10.1111/jcmm.18535\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p>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<sup>+</sup> T lymphocytes in the spleen, peripheral blood and tumour tissues. The effects of luteolin on the phenotypic and functional changes in tumour-infiltrating CD8<sup>+</sup> T lymphocytes were also investigated. Luteolin restored the cytotoxicity of tumour-infiltrating CD8<sup>+</sup> T lymphocytes in H22 tumour-bearing mice. The CD8<sup>+</sup> 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<sup>+</sup> T lymphocyte infiltration and enhance the anti-tumour effects of the PD-1 inhibitor on H22 tumour-bearing mice.</p>\",\"PeriodicalId\":101321,\"journal\":{\"name\":\"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":5.3000,\"publicationDate\":\"2024-09-12\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.18535\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1111/jcmm.18535\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","FirstCategoryId":"1085","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1111/jcmm.18535","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0
摘要
木犀草素是一种常用的传统中药,几十年来一直被用于治疗肝细胞癌(HCC)。以往的研究已经证明了它的抗肿瘤功效,但其潜在机制仍不清楚。本研究旨在评估木犀草素对 H22 肿瘤小鼠的治疗效果。木犀草素能有效抑制 HCC 小鼠模型中实体瘤的生长。高通量测序显示,叶黄素治疗可增强T细胞活化、细胞趋化和细胞因子的产生。此外,木犀草素还有助于维持脾脏、外周血和肿瘤组织中 CD8+ T 淋巴细胞的高比例。研究还探讨了叶黄素对肿瘤浸润 CD8+ T 淋巴细胞表型和功能变化的影响。在 H22 肿瘤小鼠体内,叶黄素恢复了肿瘤浸润 CD8+ T 淋巴细胞的细胞毒性。CD8+ T 淋巴细胞的表型活化增强,血清中颗粒酶 B、IFN-γ 和 TNF-α 的生成增加。叶黄素和 PD-1 抑制剂联合应用可增强 H22 肿瘤小鼠的抗肿瘤效果。叶黄素可通过诱导CD8+ T淋巴细胞浸润产生抗肿瘤免疫反应,并增强PD-1抑制剂对H22肿瘤小鼠的抗肿瘤作用。
Luteolin exerts anti-tumour immunity in hepatocellular carcinoma by accelerating CD8+ T lymphocyte infiltration
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.
期刊介绍:
The Journal of Cellular and Molecular Medicine serves as a bridge between physiology and cellular medicine, as well as molecular biology and molecular therapeutics. With a 20-year history, the journal adopts an interdisciplinary approach to showcase innovative discoveries.
It publishes research aimed at advancing the collective understanding of the cellular and molecular mechanisms underlying diseases. The journal emphasizes translational studies that translate this knowledge into therapeutic strategies. Being fully open access, the journal is accessible to all readers.