Tumors recycle glucocorticoids to drive Treg-mediated immunosuppression.
Tumors recycle glucocorticoids to drive Treg-mediated immunosuppression.
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DOI：
10.1172/jci173141
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发表时间：
2023-09-15
影响因子：
15.9
通讯作者：
Lugli, Enrico
中科院分区：
文献类型：
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作者：
Swatler, Julian;Ju, Young-Jun;Anderson, Ana C.;Lugli, Enrico
抗肿瘤免疫的抑制是肿瘤微环境的显著特征。在本期JCI中，Taves，Otsuka和作者表明，糖皮质激素（GC）是主要由肾上腺产生的强效免疫抑制激素，可以通过小鼠肿瘤细胞系表达的11β-羟基类固醇脱氢酶1（11β-HSD 1）酶从其非活性形式转化为活性代谢物。在肿瘤微环境中，GCs作用于CD 4+调节性T细胞，增强其免疫抑制功能，促进肿瘤生长。研究结果表明，靶向GC再循环作为调节肿瘤免疫抑制的策略，有可能提高免疫检查点阻断的治疗效果。
Suppression of antitumor immunity is a prominent feature of the tumor microenvironment. In this issue of the JCI, Taves, Otsuka, and authors show that glucocorticoids (GCs), which are potent immunosuppressive hormones mainly produced by the adrenals, can be reconverted from their inactive form to active metabolites via the 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) enzyme expressed by murine tumor cell lines. In the tumor microenvironment, GCs acted on CD4+ regulatory T cells to enhance their immunosuppressive function and promote tumor growth. The findings suggest that targeting GC recycling as a strategy for modulating tumor immunosuppression has the potential to improve therapeutic efficacy of immune checkpoint blockade.