Multi-omics analysis reveals the genetics and immune landscape of dexamethasone responsive genes in cancer microenvironment

Abstract

Background: Glucocorticoids, such as dexamethasone, are widely used for prevent vomiting and allergic reactions associated with cancer immunotherapy and chemotherapy. Although such use is reported to reduce the immunotherapy's efficacy, nevertheless, how dexamethasone associates with specific immune cells, particularly inside the tumor microenvironment, still remains unclear.Methods: We integrate multi-omics data, including transcriptome, mutation, copy number variation (CNV), and methylation, to explore the dexamethasone responsive genes.Results: We surprisingly found that dexamethasone responsive genes are transcriptionally down-regulated in general, where heterozygous deletion underlie such dysregulation. We further perform the pathway analysis and demonstrate that such dysregulation associates with cancer hallmarks such as epithelial-tomesenchymal transformation (EMT) activation. Next, by performing the drug sensitivity analysis, we generate a list of drugs whose efficacy potentially associates with dexamethasone response, including Methotrexate and Navitoclax. Unexpectedly, in the cancer microenvironment, dexamethasone response score positively correlates with a subset of innate immune cells. This indicates that dexamethasone potentially correlated with anti-cancer immunity in the cancer microenvironment which may be on the contrary to its systemic effect.Conclusions: Our systems-level analysis define the landscape of dexamethasone responsive genes in cancers and may serve as a useful resource for understanding the roles of dexamethasone in cancer.

Repurposing glucocorticoids as adjuvant reagents for immune checkpoint inhibitors in solid cancers

“…In the cancer microenvironment, the response score of dexamethasone is positively correlated with a subset of innate immune cells. This study indicates that dexamethasone is potentially correlated with anti-cancer immunity in the cancer microenvironment 16 .…”

“…Their study suggested that GR agonists induced miR-708 and downstream suppression of NF-kappa B signaling, which may be applicable as a novel therapeutic intervention in breast cancer treatment 15 . Shen et al 16 integrated multi-omics data to identify the responsive genes of dexamethasone and found that they were transcriptionally down-regulated. In the cancer microenvironment, the response score of dexamethasone is positively correlated with a subset of innate immune cells.…”