HLA-G 的新表达改变了肿瘤细胞系的基因程序。

IF 4.6 2区 医学 Q2 IMMUNOLOGY Cancer Immunology, Immunotherapy Pub Date : 2024-10-03 DOI:10.1007/s00262-024-03768-5
Diana Tronik-Le Roux, Marina Daouya, Isabelle Poras, François Desgrandchamps, Edgardo D Carosella
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引用次数: 0

摘要

免疫疗法的发展在临床上证明是令人鼓舞的,它可以重建因肿瘤中免疫抑制分子的表达而改变的免疫功能。然而,仍有一些患者在接受治疗后生存率很低。阐明特定 IC 在肿瘤中的新表达所引发的分子机制将是更好地理解肿瘤演变的重要一步,并有助于设计未来的临床方案。为此,我们研究了免疫检查点 HLA-G 在 ccRCC 肿瘤细胞中的新表达所引发的改变。我们首次证明,HLA-G 会改变主要与肿瘤发生、血管生成、钙流和线粒体动力学有关的关键基因。通过 CRISPR/Cas9 介导的 HLA-G 基因编辑,证实了 HLA-G 参与了 ADAM-12、NCAM1 和 NRP1 等这些通路基因的表达。这些数据揭示了 HLA-G 在肿瘤细胞中的多方面作用,远远超出了人们所熟知的 HLA-G 在免疫抗肿瘤反应中的功能。这就需要进一步研究 HLA-G 和这些新伙伴在不同来源肿瘤中的作用,以便提出未来的新疗法,改善患者的健康状况。
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HLA-G neo-expression modifies genetic programs governing tumor cell lines.

The development of immunotherapies has proved to be clinically encouraging to re-establish the immune function modified by the expression of immune inhibitory molecules in tumors. However, there are still patients with poor survival rates following treatment. The elucidation of molecular mechanisms triggered by the neo-expression of particular IC in tumors would constitute a major step toward better understanding tumor evolution and would help to design future clinical protocols. To this end, we investigate the modifications triggered by the neo-expression of the immune checkpoints HLA-G in ccRCC tumor cells. We demonstrate, for the first time, that HLA-G modifies key genes implicated mainly in tumor development, angiogenesis, calcium flow and mitochondria dynamics. The involvement of HLA-G on the expression of genes belonging to these pathways such as ADAM-12, NCAM1 and NRP1 was confirmed by the CRISPR/Cas9-mediated edition of HLA-G. The data reveal multifaceted roles of HLA-G in tumor cells which are far beyond the well-known function of HLA-G in the immune anti-tumor response. This warrants further investigation of HLA-G and these new partners in tumors of different origin so as to propose future new treatments to improve health patient's outcome.

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来源期刊
CiteScore
10.50
自引率
1.70%
发文量
207
审稿时长
1 months
期刊介绍: Cancer Immunology, Immunotherapy has the basic aim of keeping readers informed of the latest research results in the fields of oncology and immunology. As knowledge expands, the scope of the journal has broadened to include more of the progress being made in the areas of biology concerned with biological response modifiers. This helps keep readers up to date on the latest advances in our understanding of tumor-host interactions. The journal publishes short editorials including "position papers," general reviews, original articles, and short communications, providing a forum for the most current experimental and clinical advances in tumor immunology.
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