High gene expression of estrogen and progesterone receptors is associated with decreased t cell infiltration in patients with NSCLC

• Published in: Cancer treatment and research communications Vol. 27; p. 100317
• Main Authors: Oh, Michael S., Anker, Jonathan F., Chae, Young Kwang
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 2021; Elsevier
• Subjects: Aged; Carcinoma, Non-Small-Cell Lung - genetics; Carcinoma, Non-Small-Cell Lung - immunology; Carcinoma, Non-Small-Cell Lung - mortality; Datasets as Topic; Estrogen receptor; Estrogen Receptor alpha - analysis; Estrogen Receptor alpha - genetics; Estrogen Receptor beta - analysis; Estrogen Receptor beta - genetics; Female; Gene Expression Regulation, Neoplastic - immunology; Humans; Immune checkpoint; Immune Checkpoint Proteins - analysis; Immune Checkpoint Proteins - genetics; Kaplan-Meier Estimate; Lung - immunology; Lung - pathology; Lung cancer; Lung Neoplasms - genetics; Lung Neoplasms - immunology; Lung Neoplasms - mortality; Lymphocytes, Tumor-Infiltrating - immunology; Lymphocytes, Tumor-Infiltrating - metabolism; Male; Middle Aged; Progesterone receptor; Receptors, Progesterone - analysis; Receptors, Progesterone - genetics; RNA-Seq; T-Lymphocytes - immunology; T-Lymphocytes - metabolism; Tumor Microenvironment - genetics; Tumor Microenvironment - immunology; Tumor-infiltrating lymphocytes; Estrogen receptor; Immune checkpoint; Tumor-infiltrating lymphocytes; Progesterone receptor; Lung cancer
• ISSN: 2468-2942; 2468-2942
• DOI: 10.1016/j.ctarc.2021.100317

•High hormone receptor levels were associated with decreased t cell infiltration.•Findings were similar regardless of sex and tumor histology.•Estrogen receptor expression positively correlated with immune checkpoint markers. Prior studies have demonstrated that signaling via the estrogen and progesterone receptors (ER and PR) may affect prognosis in non-small cell lung cancer (NSCLC). The precise impact of hormone signaling on clinical outcomes in NSCLC, especially in the context of immune checkpoint blockade, remains unclear. We obtained RNA-Seq data from The Cancer Genome Atlas (TCGA) to determine mRNA expression levels of ESR1 (ER-α), ESR2 (ER-β), PGR (PR), CYP19A1 (aromatase), and immune-related genes. Tumor infiltration by activated T cells was predicted based on expression of immune metagenes. High levels of both ESR1 and PGR were associated with significantly decreased tumor infiltration by CD4+ and CD8+ activated T cells. CYP19A1 expression was associated with decreased CD4+ but not CD8+ T cell infiltration. There were no significant differences based on ESR2. These findings persisted after stratifying patients based on sex and tumor histology. In addition, increased ESR1 was associated with high gene expression of immune checkpoint markers, while increased PGR was associated with high levels of TGF-β genes. In a multivariate logistic regression analysis, ESR1, PGR, TGFB1, and the total number of somatic variants were identified as independent factors predicting T cell infiltration. Increased gene expression of ER-α and PR was associated with decreased activated T cell infiltration in patients with NSCLC. The relevance of hormone receptor status should be validated clinically, including in the context of immune checkpoint inhibitors.