摘要

肿瘤相关t调节细胞的免疫代谢组学

作者(年代):Subhanki达

代谢在形成癌细胞和免疫细胞之间的相互作用中起着至关重要的作用，因此最近的研究集中在肿瘤微环境中的免疫代谢这一新领域。癌细胞对有效营养物质的吸收增加，并从代谢上改变肿瘤微环境。肿瘤浸润免疫细胞往往能??T细胞适应了由癌细胞创造的葡萄糖消耗代谢环境，因此无法存活。相反，免疫抑制t调节(Treg)细胞在这种不适宜的环境中存活，并促进肿瘤免疫逃避。Treg细胞通过将其代谢偏好从葡萄糖转移到脂肪酸来适应葡萄糖匮乏的肿瘤微环境。我们的RNA-seq数据显示，Treg细胞中参与脂肪酸代谢的关键酶上调，而参与葡萄糖代谢的关键酶下调。最近的研究表明，其他的免疫细胞在脂肪酸代谢过程中，通过脂肪酸清除分子CD36来清除脂肪酸分子。有趣的是，我们观察到在CD4+ T细胞的所有亚型中，乳腺肿瘤患者的Treg细胞的CD36表达水平明显高于正常细胞。在脂肪酸摄取抑制剂的存在下，treg的生成受到阻碍，这表明CD36在这方面发挥了重要作用。 Bioinformatics analysis showed the presence of putative FOXP3-binding site at the CD36 promoter. In Treg cells FOXP3 binds to the promoter region of CD36 gene and induced its transcription which was confirmed by the bioinformatics and well as genetic ablation and biochemical studies. The genetic ablation of both FOXP3 and CD36 reduced fatty acid uptake by Treg cells and thus impaired their development and proliferation. Further extensive studies on the transcriptional control of CD36 will be pursued to elucidate the mechanism through which Treg cells metabolically adapt to the tumor microenvironment and thus to manipulate these immunosuppressive pro-tumor Treg cells to check tumor progression.