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11β 羟类固醇脱氢酶 1：预测非小细胞肺癌免疫检查点阻断治疗反应的新标志物。

11β hydroxysteroid dehydrogenase 1: a new marker for predicting response to immune-checkpoint blockade therapy in non-small-cell lung carcinoma.

机构信息

Department of Pathology, Tohoku University School of Medicine, Miyagi, Japan.

Department of Respiratory Medicine, Tohoku University Hospital, Miyagi, Japan.

出版信息

Br J Cancer. 2020 Jul;123(1):61-71. doi: 10.1038/s41416-020-0837-3. Epub 2020 Apr 27.

DOI:10.1038/s41416-020-0837-3
PMID:32336752
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7341889/
Abstract

BACKGROUND

Understanding the status of intratumoural immune microenvironment is necessary to ensure the efficacy of immune-checkpoint (IC) blockade therapy. Cortisol plays pivotal roles in glucocorticoid interactions in the immune system. We examined the correlation between intratumourally synthesised cortisol through 11β hydroxysteroid dehydrogenase (HSD) 1 and the immune microenvironment in non-small-cell lung carcinoma (NSCLC).

METHODS

We correlated 11βHSD1 immunoreactivity in 125 cases of NSCLC with the amount of intratumoural immune cells present, and 11βHSD1 immunoreactivity with the efficacy of IC blockade therapy in 18 specimens of NSCLC patients. In vitro studies were performed to validate the immunohistochemical examination.

RESULTS

11βHSD1 immunoreactivity showed a significant inverse correlation with the number of tumour-infiltrating lymphocytes and CD3- or CD8-positive T cells. 11βHSD1 immunoreactivity tended to be inversely correlated with the clinical efficacy of the IC blockade therapy. In vitro studies revealed that 11βHSD1 promoted the intratumoural synthesis of cortisol. This resulted in a decrease in cytokines and in the inhibition of monocyte migration.

CONCLUSIONS

Our study is the first report clarifying the inhibitory effects of intratumourally synthesised cortisol through 11βHSD1 on immune cell migration. We propose that the response to IC blockade therapy in NSCLC may be predicted by 11βHSD1.

摘要

背景

了解肿瘤内免疫微环境的状况对于确保免疫检查点（IC）阻断治疗的疗效是必要的。皮质醇在糖皮质激素与免疫系统的相互作用中起着关键作用。我们研究了非小细胞肺癌（NSCLC）中通过 11β 羟类固醇脱氢酶（HSD）1 合成的肿瘤内皮质醇与肿瘤内免疫微环境之间的相关性。

方法

我们将 125 例 NSCLC 中 11βHSD1 的免疫反应性与肿瘤内免疫细胞的数量相关联，并将 11βHSD1 的免疫反应性与 18 例 NSCLC 患者的 IC 阻断治疗的疗效相关联。进行了体外研究来验证免疫组织化学检查。

结果

11βHSD1 的免疫反应性与肿瘤浸润淋巴细胞和 CD3 或 CD8 阳性 T 细胞的数量呈显著负相关。11βHSD1 的免疫反应性与 IC 阻断治疗的临床疗效呈负相关趋势。体外研究表明，11βHSD1 促进了肿瘤内皮质醇的合成。这导致细胞因子减少和单核细胞迁移受到抑制。

结论

我们的研究首次阐明了肿瘤内合成的通过 11βHSD1 的皮质醇对免疫细胞迁移的抑制作用。我们提出，NSCLC 中对 IC 阻断治疗的反应可以通过 11βHSD1 来预测。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d6d/7341889/9c6abc1cb967/41416_2020_837_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d6d/7341889/7ff77c5c47aa/41416_2020_837_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d6d/7341889/4c311b38e515/41416_2020_837_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d6d/7341889/9c6abc1cb967/41416_2020_837_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d6d/7341889/7ff77c5c47aa/41416_2020_837_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d6d/7341889/4c311b38e515/41416_2020_837_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d6d/7341889/9c6abc1cb967/41416_2020_837_Fig3_HTML.jpg

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