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11β hydroxysteroid dehydrogenase 1: a new marker for predicting response to immune-checkpoint blockade therapy in non-small-cell lung carcinoma
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11β hydroxysteroid dehydrogenase 1: a new marker for predicting response to immune-checkpoint blockade therapy in non-small-cell lung carcinoma
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Journal Article
11β hydroxysteroid dehydrogenase 1: a new marker for predicting response to immune-checkpoint blockade therapy in non-small-cell lung carcinoma
2020
Overview
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.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
11-beta-Hydroxysteroid Dehydrogenase Type 1 - genetics
/ Aged
/ Biomarkers, Tumor - genetics
/ Biomedical and Life Sciences
/ Carcinoma, Non-Small-Cell Lung - genetics
/ Carcinoma, Non-Small-Cell Lung - immunology
/ Carcinoma, Non-Small-Cell Lung - pathology
/ Carcinoma, Non-Small-Cell Lung - therapy
/ CD8-Positive T-Lymphocytes - drug effects
/ CD8-Positive T-Lymphocytes - immunology
/ Cortisol
/ Female
/ Hormones
/ Humans
/ Immune Checkpoint Inhibitors - administration & dosage
/ Immune Checkpoint Inhibitors - immunology
/ Male
/ Non-small cell lung carcinoma
/ Oncology
/ Tumor Microenvironment - drug effects
/ Tumors
