Analysis of CD40 expression in breast cancer and its relation to clinicopathological characteristics.

Slobodova, Zuzana; Ehrmann, Jiří; Krejčí, Veronika; Zapletalová, J; Melichar, Bohuslav

doi:10.4149/neo_2011_03_189

Cited by 21 publications

(18 citation statements)

References 42 publications

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“…Consequently, tumor-infiltrating lymphocytes have been shown to be favorable for breast cancer survival, and UPR activation is associated with tumor-infiltrating lymphocytes in breast cancer [ 63 , 64 ]. In both the METABRIC and TCGA datasets, downregulation of genes such as CD4 and CD40 may indicate decreased CD4+ T cell response or decreased CD40 -mediated apoptosis, both of which are correlated with tumor regression, better response to therapy, and higher overall breast cancer survival [ 65 , 66 ]. Furthermore, breast tumors that overexpress AGR2 exhibit downregulation of KEGG pathways epitomized by the inflammatory response, including Pathogenic Escherichia Coli infection, HTLV-1 infection, and TNF pathway (Table 4 ).…”

Section: Discussionmentioning

confidence: 99%

Association of increased primary breast tumorAGR2with decreased disease-specific survival

et al. 2018

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ObjectiveTumor expression of Anterior Gradient 2 (AGR2), an endoplasmic reticulum protein disulfide isomerase, was associated with decreased breast cancer survival. We aimed to validate the association of tumor AGR2 mRNA expression with disease-specific survival (DSS) and identify differentially expressed signaling pathways between high and low AGR2 expression tumor groups.MethodsPrimary tumor mRNA expression data from the METABRIC study was used to evaluate AGR2 expression as a prognostic factor for DSS while adjusting for survival-determining confounders using Cox proportional-hazards regression. Differentially expressed genes and signaling pathway differences between high and low AGR2 groups were determined by modular enrichment analyses using DAVID and Ingenuity Pathway Analysis.ResultsIncreased tumor AGR2 mRNA expression was associated with decreased DSS among 1,341 women (per each standard deviation increase of AGR2 expression: HR 1.14, 95% CI: 1.01-1.29, P = 0.03). Pathway analyses supported prior experimental studies showing that estrogen receptor 1 (ESR1) regulated AGR2 expression. Canonical signaling pathways significantly differentially represented between high and low AGR2 groups included those involved in inflammation and immunity.ConclusionIncreased primary tumor AGR2 expression was associated with decreased DSS. Pathway analyses suggested that increased AGR2 was associated with endoplasmic reticular homeostasis, possibly allowing tumor cells to overcome hypoxic stress and meet the increased protein demand of tumorigenesis, thereby preventing unfolded protein response-mediated apoptosis.

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Section: Discussionmentioning

confidence: 99%

Association of increased primary breast tumorAGR2with decreased disease-specific survival

et al. 2018

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“…CD40 stimulation by its soluble recombinant human CD40 ligand directly inhibits human breast cancer cells in vitro and in SCID mice model [ 84 ]. A clinical study reported a significant difference in expression of cytoplasmic CD40 between breast cancer subtypes, and cytoplasmic expression of CD40 is related to a better prognosis [ 85 ], which suggest that CD40 may have potential as a new prognostic factor in breast cancer.…”

Section: Stimulatory Molecule Agonist Antibodiesmentioning

confidence: 99%

New Immunotherapy Strategies in Breast Cancer

Tang

Zhang

et al. 2017

IJERPH

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Breast cancer is the most commonly diagnosed cancer among women. Therapeutic treatments for breast cancer generally include surgery, chemotherapy, radiotherapy, endocrinotherapy and molecular targeted therapy. With the development of molecular biology, immunology and pharmacogenomics, immunotherapy becomes a promising new field in breast cancer therapies. In this review, we discussed recent progress in breast cancer immunotherapy, including cancer vaccines, bispecific antibodies, and immune checkpoint inhibitors. Several additional immunotherapy modalities in early stages of development are also highlighted. It is believed that these new immunotherapeutic strategies will ultimately change the current status of breast cancer therapies.

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“…CD40 expression is associated with clinical stage, degree of metastasis and poor prognosis in melanoma [13], gastric cancer [14], and non-small cell lung cancer [15]. In contrast, CD40, frequently expressed on tumor-associated macrophages, is associated with favorable prognosis in colorectal cancer [16], head and neck squamous cell carcinoma [17] and breast cancer [18]. Furthermore, CD40 ligation strongly inhibited breast cancer growth [19] and induced ovarian cancer [20] and colon cancer cell [21] apoptosis.…”

Section: Introductionmentioning

confidence: 99%

CD40 expression in renal cell carcinoma is associated with tumor apoptosis, CD8+ T cell frequency and patient survival

et al. 2014

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The co-stimulatory molecule, CD40, is expressed in renal cell carcinoma (RCC) and a variety of inflammatory diseases in the kidney. We investigated the relationship between tumor-associated CD40 expression, immune milieu of the tumor microenvironment, tumor stage and survival of patients with RCC. The expression of CD40, TUNEL and CD8 in human renal cell carcinomas was analyzed by immunohistochemistry performed on tissue samples obtained at the time of surgery. Computer-assisted quantitation of protein expression was used to analyze results in connection with patient survival and tumor stage. We show for the first time that tumor-associated CD40 expression is associated with prolonged survival in RCC patients. Tumor apoptosis (TUNEL) and CD8 immunostaining were also associated with patient survival. No relation was observed between CD40 expression and tumor stage. Our results suggest CD40 may be a prognostic biomarker indicative of prolonged RCC patient survival. Strategies that up-regulate CD40 expression in some RCC patients may thus improve survival, supporting further studies of agonistic CD40 antibodies in RCC.

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Analysis of CD40 expression in breast cancer and its relation to clinicopathological characteristics.

Cited by 21 publications

References 42 publications

Association of increased primary breast tumorAGR2with decreased disease-specific survival

Association of increased primary breast tumorAGR2with decreased disease-specific survival

New Immunotherapy Strategies in Breast Cancer

CD40 expression in renal cell carcinoma is associated with tumor apoptosis, CD8+ T cell frequency and patient survival

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