肿瘤细胞消耗牛磺酸会耗尽 CD8+ T 细胞

IF 67.7 1区医学 Q1 IMMUNOLOGY

Nature Reviews Immunology Pub Date : 2024-04-17 DOI:10.1038/s41577-024-01032-6

Alexandra Flemming

引用次数: 0

摘要

氨基酸牛磺酸是市场上销售的一种营养补充剂。Cao 等人的研究表明，牛磺酸不仅能增强癌细胞的恶性行为，还能提高 CD8+ T 细胞的存活率和效应功能。在胃癌和黑色素瘤小鼠模型中，瘤内注射牛磺酸可促进免疫功能低下小鼠的肿瘤生长，但抑制免疫功能正常小鼠的肿瘤生长。进一步的分析表明，肿瘤细胞通过膜转运体 SLC6A6 消耗牛磺酸，而 SLC6A6 的表达是不同类型癌症的一个负面预后指标。作者发现，肿瘤细胞可以通过过表达 SLC6A6 来竞争 CD8+ T 细胞的牛磺酸，从而诱导 CD8+ T 细胞的内质网（ER）应激。这会促进转录因子 ATF4 的表达，从而上调免疫检查点基因并诱导 T 细胞衰竭。给小鼠补充牛磺酸能抑制 ATF4 的转录，促进 CD8+ T 细胞的存活和功能。在胃癌小鼠模型中，化疗会上调癌细胞中的 SLC6A6。然而，补充牛磺酸可提高化疗的疗效，这表明牛磺酸重新激活 CD8+ T 细胞的能力超过了其直接促进肿瘤的作用。目前已启动一项临床试验，测试胃癌患者口服牛磺酸与化疗或免疫疗法的联合治疗效果。

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Tumour cell consumption of taurine exhausts CD8+ T cells

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来源期刊

Nature Reviews Immunology 医学-免疫学

CiteScore

93.40

自引率

0.40%

发文量

131

审稿时长

6-12 weeks

期刊介绍： Nature Reviews Immunology is a journal that provides comprehensive coverage of all areas of immunology, including fundamental mechanisms and applied aspects. It has two international standard serial numbers (ISSN): 1474-1733 for print and 1474-1741 for online. In addition to review articles, the journal also features recent developments and new primary papers in the field, as well as reflections on influential people, papers, and events in the development of immunology. The subjects covered by Nature Reviews Immunology include allergy and asthma, autoimmunity, antigen processing and presentation, apoptosis and cell death, chemokines and chemokine receptors, cytokines and cytokine receptors, development and function of cells of the immune system, haematopoiesis, infection and immunity, immunotherapy, innate immunity, mucosal immunology and the microbiota, regulation of the immune response, signalling in the immune system, transplantation, tumour immunology and immunotherapy, and vaccine development.