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Intratumoral Administration of a Novel Cytotoxic Formulation with Strong Tissue Dispersive Properties Regresses Tumor Growth and Elicits Systemic Adaptive Immunity in In Vivo Models
Open AccessArticle

Contribution of Immune Cells to Glucocorticoid Receptor Expression in Breast Cancer

1
Department of Medical Oncology, Roswell Park Comprehensive Cancer Center, Elm & Carlton Streets, Buffalo, NY 14263, USA
2
Department of Medical Oncology, University of Alabama, Birmingham, AL 35294, USA
3
Breast Surgery, Department of Surgical Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA
4
Departments of Surgery, Yokohama City University, Yokohama 236-0004, Japan
5
Department of Immunology, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA
6
Division of Medical Oncology, Washington University, St. Louis, MO 63130, USA
7
Department of Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8510, Japan
8
Department of Breast Surgery and Oncology, Tokyo Medical University, Tokyo 160-8402, Japan
9
Department of Breast Surgery, Fukushima Medical University, Fukushima 960-1295, Japan
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2020, 21(13), 4635; https://doi.org/10.3390/ijms21134635
Received: 26 May 2020 / Revised: 29 June 2020 / Accepted: 29 June 2020 / Published: 30 June 2020
(This article belongs to the Special Issue The Immune Landscape in Solid Tumors)
Breast cancer (BC) patients experience increased stress with elevated cortisol levels, increasing risk of cancer recurrence. Cortisol binds to a cytoplasmic receptor, glucocorticoid receptor (GR) encoded by GR gene (NR3C1). We hypothesized that not only cancer cells, but even immune cells in the tumor microenvironment (TME) may contribute to GR expression in bulk tumor and influence prognosis. To test this, mRNA expression data was accessed from METABRIC and TCGA. “High” and “low” expression was based on highest and lowest quartiles of NR3C1 gene expression, respectively. Single-cell sequencing data were obtained from GSE75688 and GSE114725 cohorts. Computer algorithms CIBERSORT, Gene Set Enrichment Analysis and TIMER were used. GR-high BC has better median disease-free and disease-specific survival. Single cell sequencing data showed higher GR expression on immune cells compared to cancer and stromal cells. Positive correlation between GR-high BC and CD8+ T-cells was noted. In GR-high tumors, higher cytolytic activity (CYT) with decreased T-regulatory and T-follicular helper cells was observed. High GR expression was associated with lower proliferation index Ki67, enriched in IL-2_STAT5, apoptosis, KRAS, TGF-β signaling, and epithelial-to-mesenchymal transition. Immune cells significantly contribute to GR expression of bulk BC. GR-high BC has a favorable TME with higher CYT with favorable outcomes. View Full-Text
Keywords: glucocorticoid receptor; breast cancer; NR3C1; immune cells; TCGA; METABRIC; CIBERSORT glucocorticoid receptor; breast cancer; NR3C1; immune cells; TCGA; METABRIC; CIBERSORT
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Gandhi, S.; Elkhanany, A.; Oshi, M.; Dai, T.; Opyrchal, M.; Mohammadpour, H.; Repasky, E.A.; Takabe, K. Contribution of Immune Cells to Glucocorticoid Receptor Expression in Breast Cancer. Int. J. Mol. Sci. 2020, 21, 4635.

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