Dataset Information

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

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.

SUBMITTER: Song IH

PROVIDER: S-EPMC9582481 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Song In Hye IH Kim Young-Ae YA Heo Sun-Hee SH Bang Won Seon WS Park Hye Seon HS Choi Yeon Ho YH Lee Heejae H Seo Jeong-Han JH Cho Youngjin Y Jung Sung Wook SW Kim Hee Jeong HJ Ahn Sei Hyun SH Lee Hee Jin HJ Gong Gyungyub G

Cancer research and treatment 20211221 4

<h4>Purpose</h4>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.<h4>Materials and methods</h ...[more]

PMID: 34942685

Similar Datasets

Project description:Low doses of anticancer drugs have been shown to enhance antitumor immune response and increase the efficacy of immunotherapy. The molecular basis for such effects remains elusive, although selective depletion of T regulatory cells has been demonstrated. In the current studies, we demonstrate that topotecan (TPT), a topoisomerase I-targeting drug with a well-defined mechanism of action, stimulates major histocompatibility complex class I (MHC I) expression in breast cancer cells through elevated expression/secretion of interferon-? (IFN-?) and activation of type I IFN signaling. First, we show that TPT treatment elevates the expression of both total and cell-surface MHC I in breast cancer cells. Second, conditioned media from TPT-treated breast cancer ZR-75-1 cells induce elevated expression of cell-surface MHC I in drug-naïve recipient cells, suggesting the involvement of cytokines and/or other secreted molecules. Consistently, TPT-treated cells exhibit elevated expression of multiple cytokines such as IFN-?, TNF-?, IL-6 and IL-8. Third, either knocking down the type I interferon receptor subunit 1 (IFNAR1) or addition of neutralizing antibody against IFN-? results in reduced MHC I expression in TPT-treated cells. Together, these results suggest that TPT induces increased IFN-? autocrine/paracrine signaling through type I IFN receptor, resulting in the elevated MHC I expression in tumor cells. Studies have also demonstrated that other chemotherapeutic agents (e.g. etoposide, cisplatin, paclitaxel and vinblastine) similarly induce increased IFN-? secretion and elevated MHC I expression. In addition, conditioned media from ?-irradiated donor cells are shown to induce IFN-?-dependent MHC I expression in unirradiated recipient cells. In the aggregate, our results suggest that many cancer therapeutics induce elevated tumor antigen presentation through MHC I, which could represent a common mechanism for enhanced antitumor immune response through T cell cytotoxicity during metronomic chemotherapy, as well as increased efficacy of combined chemo- (or radio-)/immuno-therapy.

Dataset Information

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

Purpose

Materials and methods

Results

Conclusion

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets