The Association of Estrogen Receptor Activity, Interferon Signaling, and MHC Class I Expression in Breast Cancer
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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.
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.
참고문헌 (28)
- Loi S, "Prognostic and predictive value of tumor-infiltrating lymphocytes in a phase III randomized adjuvant breast cancer trial in node-positive breast cancer comparing the addition of docetaxel to doxorubicin with doxorubicin-based chemotherapy : BIG 02-98", J Clin Oncol, 31, pp.860~867 (2013)
- Denkert C, "Tumor-associated lymphocytes as an independent predictor of response to neoadjuvant chemotherapy in breast cancer", J Clin Oncol, 28, pp.105~113 (2010)
- 이희진, "Tumor-Associated Lymphocytes Predict Response to Neoadjuvant Chemotherapy in Breast Cancer Patients", Journal of Breast Cancer, 16(1), pp.32~39 (2013), 한국유방암학회[DOI]
- Seo AN, "Tumour-infiltrating CD8+ lymphocytes as an independent predictive factor for pathological complete response to primary systemic therapy in breast cancer", Br J Cancer, 109, pp.2705~2713 (2013)
- Adams S, "Prognostic value of tumor-infiltrating lymphocytes in triple-negative breast cancers from two phase III randomized adjuvant breast cancer trials : ECOG 2197 and ECOG 1199", J Clin Oncol, 32, pp.2959~2966 (2014)
- Phan GQ, "Adoptive cell transfer for patients with metastatic melanoma : the potential and promise of cancer immunotherapy", Cancer Control, 20, pp.289~297 (2013)
- Agrawal S, "MHC class I gene expression and regulation", J Hematother Stem Cell Res, 9, pp.795~812 (2000)
- Torigoe T, "Establishment of a monoclonal anti-pan HLA class I antibody suitable for immunostaining of formalin-fixed tissue : unusually high frequency of down-regulation in breast cancer tissues", Pathol Int, 62, pp.303~308 (2012)
- Sistigu A, "Cancer cell-autonomous contribution of type I interferon signaling to the efficacy of chemotherapy", Nat Med, 20, pp.1301~1309 (2014)
- Lee HJ, "Differential expression of major histocompatibility complex class I in subtypes of breast cancer is associated with estrogen receptor and interferon signaling", Oncotarget, 7, pp.30119~30132 (2016)
- Lee HJ, "Prognostic significance of tumor-infiltrating lymphocytes and the tertiary lymphoid structures in HER2-positive breast cancer treated with adjuvant trastuzumab", Am J Clin Pathol, 144, pp.278~288 (2015)
- Kim YA, "MxA expression is associated with tumor-infiltrating lymphocytes and is a prognostic factor in triple-negative breast cancer", Breast Cancer Res Treat, 156, pp.597~606 (2016)
- Al Saleh S, "Estrogen receptor silencing induces epithelial to mesenchymal transition in human breast cancer cells", PLoS One, 6, pp.e20610~ (2011)
- Kim HJ, "Efficacy of neoadjuvant endocrine therapy compared with neoadjuvant chemotherapy in pre-menopausal patients with oestrogen receptor-positive and HER2-negative, lymph node-positive breast cancer", Breast Cancer Res, 22, pp.54~ (2020)
- Allison KH, "WHO classification of tumours: breast tumours" (2019), IARC Press
- Salgado R, "The evaluation of tumor-infiltrating lymphocytes(TILs)in breast cancer : recommendations by an International TILs Working Group 2014", Ann Oncol, 26, pp.259~271 (2015)
- Ogston KN, "A new histological grading system to assess response of breast cancers to primary chemotherapy : prognostic significance and survival", Breast, 12, pp.320~327 (2003)
- Formenti SC, "Low HER2", neu gene expression is associated with pathological response to concurrent paclitaxel and radiation therapy in locally advanced breast cancer, 2002, pp.52, 397~405
- R Core Team, "R: a language and environment for statistical computing. 3.2.3 ed", R Foundation for Statistical Computing, ~ (2015)
- 송인혜, "Predictive Value of Tertiary Lymphoid Structures Assessed by High Endothelial Venule Counts in the Neoadjuvant Setting of Triple-Negative Breast Cancer", Cancer Research and Treatment, 49(2), pp.399~407 (2017), 대한암학회
- Wimberly H, "PD-L1 expression correlates with tumor-infiltrating lymphocytes and response to neoadjuvant chemotherapy in breast cancer", Cancer Immunol Res, 3, pp.326~332 (2015)
- Stanton SE, "Clinical significance of tumor-infiltrating lymphocytes in breast cancer", J Immunother Cancer, 4, pp.59~ (2016)
- Berger ER, "Immunotherapy treatment for triple negative breast cancer", Pharmaceuticals(Basel), 14, pp.763~ (2021)
- Spranger S, "Density of immunogenic antigens does not explain the presence or absence of the T-cell-inflamed tumor microenvironment in melanoma", Proc Natl Acad Sci U S A, 113, pp.E7759~E7768 (2016)
- Mostafa AA, "Activation of ERalpha signaling differentially modulates IFN-gamma induced HLA-class II expression in breast cancer cells", PLoS One, 9, pp.e87377~ (2014)
- Anandappa AJ, "Directing traffic : how to effectively drive T cells into tumors", Cancer Discov, 10, pp.185~197 (2020)
- Castaneda CA, "Tumor infiltrating lymphocytes in triple negative breast cancer receiving neoadjuvant chemotherapy", World J Clin Oncol, 7, pp.387~394 (2016)
- Park YH, "Chemotherapy induces dynamic immune responses in breast cancers that impact treatment outcome", Nat Commun, 11, pp.6175~ (2020)