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Clinical Significance of Tumor Infiltrating Lymphocytes in Association with Hormone Receptor Expression Patterns in Epithelial Ovarian Cancer

Authors
 Gwan Hee Han  ;  Ilseon Hwang  ;  Hanbyoul Cho  ;  Kris Ylaya  ;  Jung-A Choi  ;  Hyunja Kwon  ;  Joon-Yong Chung  ;  Stephen M Hewitt  ;  Jae-Hoon Kim 
Citation
 INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, Vol.22(11) : 5714, 2021-05 
Journal Title
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
ISSN
 1661-6596 
Issue Date
2021-05
MeSH
B7-H1 Antigen / genetics ; Biomarkers, Tumor* ; Carcinoma, Ovarian Epithelial / etiology* ; Carcinoma, Ovarian Epithelial / metabolism ; Carcinoma, Ovarian Epithelial / pathology ; Computational Biology / methods ; Databases, Genetic ; Disease Susceptibility ; Female ; Gene Expression ; Humans ; Immunohistochemistry ; Lymphocytes, Tumor-Infiltrating / immunology* ; Lymphocytes, Tumor-Infiltrating / metabolism* ; Lymphocytes, Tumor-Infiltrating / pathology ; Ovarian Neoplasms / etiology* ; Ovarian Neoplasms / metabolism ; Ovarian Neoplasms / pathology ; Programmed Cell Death 1 Receptor / genetics ; Receptors, Steroid / genetics* ; Receptors, Steroid / metabolism ; Tumor Microenvironment / genetics ; Tumor Microenvironment / immunology
Keywords
epithelial ovarian cancer ; hormone receptors ; regulatory T cell ; triple dominant group ; tumor infiltrating lymphocytes
Abstract
Hormone receptor expression patterns often correlate with infiltration of specific lymphocytes in tumors. Specifically, the presence of specific tumor-infiltrating lymphocytes (TILs) with particular hormone receptor expression is reportedly associated with breast cancer, however, this has not been revealed in epithelial ovarian cancer (EOC). Therefore, we investigated the association between hormone receptor expression and TILs in EOC. Here we found that ERα, AR, and GR expression increased in EOC, while PR was significantly reduced and ERβ expression showed a reduced trend compared to normal epithelium. Cluster analysis indicated poor disease-free survival (DFS) in AR+/GR+/PR+ subgroup (triple dominant group); while the Cox proportional-hazards model highlighted the triple dominant group as an independent prognostic factor for DFS. In addition, significant upregulation of FoxP3+ TILs, PD-1, and PD-L1 was observed in the triple dominant group compared to other groups. NanoString analyses further suggested that tumor necrosis factor (TNF) and/or NF-κB signaling pathways were activated with significant upregulation of RELA, MAP3K5, TNFAIP3, BCL2L1, RIPK1, TRAF2, PARP1, and AKT1 in the triple dominant EOC group. The triple dominant subgroup correlates with poor prognosis in EOC. Moreover, the TNF and/or NF-κB signaling pathways may be responsible for hormone-mediated inhibition of the immune microenvironment.
Files in This Item:
T202102064.pdf Download
DOI
10.3390/ijms22115714
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Obstetrics and Gynecology (산부인과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Jae Hoon(김재훈) ORCID logo https://orcid.org/0000-0001-6599-7065
Cho, Hanbyoul(조한별) ORCID logo https://orcid.org/0000-0002-6177-1648
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/184083
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