High IRF8 expression correlates with CD8 T cell infiltration and is a predictive biomarker of therapy response in ER-negative breast cancer.
Background: Characterization of breast cancer (BC) through the determination of conventional markers such as ER, PR, HER2, and Ki67 has been useful as a predictive and therapeutic tool. Also, assessment of tumor-infiltrating lymphocytes has been proposed as an important prognostic aspect to be consi...
| Publicado en: | Breast Cancer Research Vol. 23; no. 1; pp. 1 - 16 |
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| Autores principales: | , , , , , , , , , , , , , |
| Formato: | research Journal Article |
| Publicado: |
BioMed Central
4/22/2021
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=149947292&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 149947292 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 14655411 8UYJ jtl: Breast Cancer Research issn: 14655411 maglogo: N pubinfo: dt: 4/22/2021 vid: 23 iid: 1 pid: 24147 pub: BioMed Central artinfo: ui: 149947292 149947292 NLM33766090 149947292 10.1186/s13058-021-01418-7 NLM33766090 149947292 ppf: 1 ppct: 15 formats: fmt: – @attributes: type: T – @attributes: type: P tig: atl: High IRF8 expression correlates with CD8 T cell infiltration and is a predictive biomarker of therapy response in ER-negative breast cancer. aug: au: Gatti, Gerardo Betts, Courtney Rocha, Darío Nicola, Maribel Grupe, Verónica Ditada, Cecilia Nuñez, Nicolas G. Roselli, Emiliano Araya, Paula Dutto, Jeremías Boffelli, Lucia Fernández, Elmer Coussens, Lisa M. Maccioni, Mariana affil: Laboratorio de Investigación en Cáncer, Fundación para el progreso de la Medicina, X5000EMS, Córdoba, Argentina sug: subj: Proteins Proteins Metabolism Lymphocytes Pathology T Lymphocytes Pathology Breast Neoplasms Metabolism Prognosis Breast Neoplasms Therapy Treatment Outcomes Breast Neoplasms Pathology Cell Line, Tumor Human Female Disease Progression Comparative Studies Multicenter Studies Evaluation Research Validation Studies Clinical Assessment Tools Scales Female ab: Background: Characterization of breast cancer (BC) through the determination of conventional markers such as ER, PR, HER2, and Ki67 has been useful as a predictive and therapeutic tool. Also, assessment of tumor-infiltrating lymphocytes has been proposed as an important prognostic aspect to be considered in certain BC subtypes. However, there is still a need to identify additional biomarkers that could add precision in distinguishing therapeutic response of individual patients. To this end, we focused in the expression of interferon regulatory factor 8 (IRF8) in BC cells. IRF8 is a transcription factor which plays a well-determined role in myeloid cells and that seems to have multiple antitumoral roles: it has tumor suppressor functions; it acts downstream IFN/STAT1, required for the success of some therapeutic regimes, and its expression in neoplastic cells seems to depend on a cross talk between the immune contexture and the tumor cells. The goal of the present study was to examine the relationship between IRF8 with the therapeutic response and the immune contexture in BC, since its clinical significance in this type of cancer has not been thoroughly addressed.Methods: We identified the relationship between IRF8 expression and the clinical outcome of BC patients and validated IRF8 as predictive biomarker by using public databases and then performed in silico analysis. To correlate the expression of IRF8 with the immune infiltrate in BC samples, we performed quantitative multiplex immunohistochemistry.Results: IRF8 expression can precisely predict the complete pathological response to monoclonal antibody therapy or to select combinations of chemotherapy such as FAC (fluorouracil, adriamycin, and cytoxan) in ER-negative BC subtypes. Analysis of immune cell infiltration indicates there is a strong correlation between activated and effector CD8+ T cell infiltration and tumoral IRF8 expression.Conclusions: We propose IRF8 expression as a potent biomarker not only for prognosis, but also for predicting therapy response in ER-negative BC phenotypes. Its expression in neoplastic cells also correlates with CD8+ T cell activation and infiltration. Therefore, our results justify new efforts towards understanding mechanisms regulating IRF8 expression and how they can be therapeutically manipulated. pubtype: Academic Journal doctype: research Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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