The Association of Estrogen Receptor Activity, Interferon Signaling, and MHC Class I Expression in Breast Cancer

Overview

Journal Cancer Res Treat

Specialty Oncology

Date 2021 Dec 23

PMID 34942685

Citations 2

Authors

In Hye Song

Young-Ae Kim

Sun-Hee Heo

Won Seon Bang

Hye Seon Park

Yeon Ho Choi

Heejae Lee

Jeong-Han Seo

Youngjin Cho

Sung Wook Jung

Hee Jeong Kim

Sei Hyun Ahn

Hee Jin Lee

Gyungyub Gong

Affiliations

Soon will be listed here.

Abstract

Purpose: The expression of major histocompatibility complex class I (MHC I) has previously been reported to be negatively associated with estrogen receptor (ER) expression. Furthermore, MHC I expression, level of tumor-infiltrating lymphocytes (TILs), and expression of interferon (IFN) mediator MxA are positively associated with one another in human breast cancers. This study aimed to investigate the mechanisms of association of MHC I with ER and IFN signaling.

Materials And Methods: The human leukocyte antigen (HLA)-ABC protein expression was analyzed in breast cancer cell lines. The expressions of HLA-A and MxA mRNAs were analyzed in MCF-7 cells in Gene Expression Omnibus (GEO) data. ER and HLA-ABC expressions, Ki-67 labeling index and TIL levels in tumor tissue were also analyzed in ER+/ human epidermal growth factor receptor 2 (HER2)- breast cancer patients who randomly received either neoadjuvant chemotherapy or estrogen modulator treatment followed by resection.

Results: HLA-ABC protein expression was decreased after β-estradiol treatment or hESR-GFP transfection and increased after fulvestrant or IFN-γ treatment in cell lines. In GEO data, HLA-A and MxA expression was increased after ESR1 shRNA transfection. In patients, ER Allred score was significantly lower and the HLA-ABC expression, TIL levels, and Ki-67 were significantly higher in the estrogen modulator treated group than the chemotherapy treated group.

Conclusion: MHC I expression and TIL levels might be affected by ER pathway modulation and IFN treatment. Further studies elucidating the mechanism of MHC I regulation could suggest a way to boost TIL influx in cancer in a clinical setting.

Citing Articles

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Hormone Receptor Signaling and Breast Cancer Resistance to Anti-Tumor Immunity.

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