Cancer–testis antigen expression in triple-negative breast cancer

Curigliano, Giuseppe; Viale, Giuseppe; Ghioni, Mariacristina; Jungbluth, Achim A.; Bagnardi, Vincenzo; Spagnoli, G.C.; Neville, A. Munro; Nolè, Franco; Rotmensz, Nicole; Goldhirsch, A.

doi:10.1093/annonc/mdq325

Cited by 86 publications

(89 citation statements)

References 37 publications

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“…A series of studies have been committed to evaluate MAGE-A expression in breast cancer cases with specific biomarkers. Curigliano et al [27] assessed expression of MAGE-A in 50 ER (+) /HER-2 (-) and 50 TN cases by IHC method. They found 32% TN cases with higher intensity of MAGE-A, while 18% ER (+) cases were positive for MAGE-A with lower intensity.…”

Section: Discussionmentioning

confidence: 99%

“…Also, MAGE-A-positive cases were often with high histological grade and metastatic axillary lymph nodes, which strengthened the association between MAGE-A and cancer progression. According to some studies, MAGE-A proteins have to do with negative hormone receptor status, high histologic grade [37,39], large tumor size (≥2cm) [36], positive sentinel lymph nodes (SLN) [40], high Ki-67 score [27] and HER-2 negativity. Notably, MAGE-A expression is contributed to unfavorable outcomes and cancer development.…”

Section: Discussionmentioning

confidence: 99%

“…Accumulating evidence showed that MAGE-A expression is accused for tumor growth and progress [23][24][25][26]. Moreover, MAGE-A expression is detected frequently in TNBC patients [27].…”

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confidence: 99%

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MAGE-A is frequently expressed in triple negative breast cancer and associated with epithelial-mesenchymal transition

Wang¹,

Sang²,

Geng³

et al. 2016

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Epithelial-mesenchymal transition (EMT) is a crucial step in tumor metastasis. Triple negative (TN) breast cancer, a high metastasis phenotype, has been verified to be associated with EMT. Melanoma associated antigen-A (MAGE-A) is exclusively expressed in cancers with high aggressiveness as well as unfavorable prognosis and likely to be associated with EMT of triple negative breast cancer (TNBC). The aim of the study is to analyze the expression profile of MAGE-A in breast cancer and the correlation between MAGE-A and EMT of TNBC. Immunohistochemistry (IHC) was performed to assess the prevalence of MAGE-A, vimentin, E-cadherin and β-catenin in breast cancer tissues and correlate them with clinical pathological parameters. The association between MAGE-A and EMT markers was also evaluated. Scratch assay and transwell invasion assay were carried out to evaluate the impact of MAGE-A down-regulation on migration and invasion of the breast cancer cells. Real-time PCR was also conducted to evaluate alterations in EMT markers with decrease in MAGE-A. The results showed that MAGE-A was absent in normal tissue but expressed in tumor samples with the incidence of 49.17% (P=0.008). MAGE-A staining was higher in TNBC (76.47%, 13/17), followed by HER-2(+) (53.85%, 7/13) and Luminal set (43.33%, 39/90), and it was significantly correlated with ER (-), PR (-), HER-2 (-), lymph nodes involvement and higher histological grade (P<0.05). E-cadherin-positivity was frequent in Luminal set (94.44%, 85/90) and linked to ER (+), negative lymph nodes and lower histological grade (P<0.05). Vimentin expression was often observed in TNBC (70.59%, 12/17) and ER (-), PR (-), lymph nodes (+) groups (P<0.05). Expression of β-catenin was prevalent in Luminal set (93.33%, 84/90) and correlated with ER (+), PR (+) and lower histological grade (P<0.05). MAGE-A was inversely associated with E-cadherin (P=0.011) and β-catenin (P=0.048) but expressed in the same trend with vimentin (P=0.000). Migration and invasion of MDA-MB-231 were inhibited when MAGE-A decreased. Increase in epithelial markers and decline in mesenchymal indicators were also seen with MAGE-A reduction. Snail, Slug, ZEB1 and ZEB2 were also down-regulated. In conclusion, MAGE-A may be responsible for high aggressiveness and EMT of TNBC and can be a new choice for targeted therapy.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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MAGE-A is frequently expressed in triple negative breast cancer and associated with epithelial-mesenchymal transition

Wang¹,

Sang²,

Geng³

et al. 2016

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“…Previous studies have demonstrated that some CTA such as MAGE and NY-ESO-1 are expressed relatively high in triplenegative breast cancer which is of limited therapeutic options (11). The SSX protein family is a potential target applicable to many types of cancer instead of tumors of a restricted histological type (25).…”

Section: Discussionmentioning

confidence: 99%

“…Up to now, only a few CTAs have been shown to elicit both humoral and cell-mediated immune responses in human, including SSX, MAGE-A, and NY-ESO-1 (10). MAGE-A and NY-ESO-1 are expressed in a substantial proportion of triple-negative breast cancers (11). It is also reported that SSX2 is found in breast cancer patients.…”

Section: Introductionmentioning

confidence: 99%

Cancer/testis antigen SSX2 enhances invasiveness in MCF-7 cells by repressing ERα signaling

et al. 2012

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Abstract. Cancer/testis antigen (CTA) SSX2, which is silent in most normal adult tissues and expressed in various malignant tumors, has been identified for decades. Expression of SSX in tumors has been associated with advanced stages and worse patient prognosis. However, little is known about its role in breast cancer. The SSX2 expression plasmid constructed was stably transfected into the breast cancer cell line MCF-7. The influence of SSX2 on MCF-7 cells was assessed using MTT assay, flow cytometry, transwell invasion assay and in vivo tumorigenicity assay. A comparative proteomic approach was performed to identify and clarify the underlying molecular mechanisms. SSX2 expression was more pronounced in ERα-negative breast cancer cells compared with the positive ones. Overexpression of SSX2 induced cell growth and prompted cell invasion. Both ERα and E-cadherin expression were suppressed in the SSX2 overexpressing MCF-7 cells. Eleven known proteins were identified with significant differential expression. Among these, five were decreased, while other six were increased in the SSX2 overexpressing MCF-7 cells. These results suggested SSX2 may enhance invasiveness in MCF-7 cells both in vivo and in vitro. The regulation of ERα signaling by target proteins of SSX2 may explain the metastatic potential of breast cancer cells.

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Curcumin improves the therapeutic efficacy of Listeria^at‐Mage‐b vaccine in correlation with improved T‐cell responses in blood of a triple‐negative breast cancer model 4T1

et al. 2013

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Success of cancer vaccination is strongly hampered by immune suppression in the tumor microenvironment (TME). Interleukin (IL)-6 is particularly and highly produced by triple-negative breast cancer (TNBC) cells, and has been considered as an important contributor to immune suppression in the TME. Therefore, we hypothesized that IL-6 reduction may improve efficacy of vaccination against TNBC cancer through improved T-cell responses. To prove this hypothesis, we investigated the effect of curcumin, an inhibitor of IL-6 production, on vaccination of a highly attenuated Listeria monocytogenes (Listeriaat), encoding tumor-associated antigens (TAA) Mage-b in a TNBC model 4T1. Two therapeutic vaccination strategies with Listeriaat-Mage-b and curcumin were tested. The first immunization strategy involved all Listeriaat-Mage-b vaccinations and curcumin after tumor development. As curcumin has been consumed all over the world, the second immunization strategy involved curcumin before and all therapeutic vaccinations with Listeriaat-Mage-b after tumor development. Here, we demonstrate that curcumin significantly improves therapeutic efficacy of Listeriaat-Mage-b with both immunization strategies particularly against metastases in a TNBC model (4T1). The combination therapy was slightly but significantly more effective against the metastases when curcumin was administered before compared to after tumor development. With curcumin before tumor development in the combination therapy, the production of IL-6 was significantly decreased and IL-12 increased by myeloid-derived suppressor cells (MDSC), in correlation with improved CD4 and CD8 T-cell responses in blood. Our study suggests that curcumin improves the efficacy of Listeriaat-Mage-b vaccine against metastases in TNBC model 4T1 through reversal of tumor-induced immune suppression.This study is focused on improving cancer vaccination by reducing immune suppression. Here we demonstrate that curcumin improves vaccine efficacy of Listeria-Mage-b by converting myeloid-derived suppressor cells into an immune stimulating phenotype, that is, through reducing IL-6 and increasing IL-12 production, in correlation with improved T cell responses and a dramatic reduction in the number of metastases. The novel results of this study may be a platform for improvement of other cancer vaccines by curcumin.

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Cancer–testis antigen expression in triple-negative breast cancer

Abstract: MAGE-A and NY-ESO-1 CT antigens are expressed in a substantial proportion of TN breast cancers. Because of the limited therapeutic options for this group of patients, CT antigen-based vaccines might prove to be useful for patients with this phenotype of breast cancer.

Cited by 86 publications

References 37 publications

MAGE-A is frequently expressed in triple negative breast cancer and associated with epithelial-mesenchymal transition

MAGE-A is frequently expressed in triple negative breast cancer and associated with epithelial-mesenchymal transition

Cancer/testis antigen SSX2 enhances invasiveness in MCF-7 cells by repressing ERα signaling

Curcumin improves the therapeutic efficacy of Listeria^at‐Mage‐b vaccine in correlation with improved T‐cell responses in blood of a triple‐negative breast cancer model 4T1

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Cancer–testis antigen expression in triple-negative breast cancer

Abstract: MAGE-A and NY-ESO-1 CT antigens are expressed in a substantial proportion of TN breast cancers. Because of the limited therapeutic options for this group of patients, CT antigen-based vaccines might prove to be useful for patients with this phenotype of breast cancer.

Cited by 86 publications

References 37 publications

MAGE-A is frequently expressed in triple negative breast cancer and associated with epithelial-mesenchymal transition

MAGE-A is frequently expressed in triple negative breast cancer and associated with epithelial-mesenchymal transition

Cancer/testis antigen SSX2 enhances invasiveness in MCF-7 cells by repressing ERα signaling

Curcumin improves the therapeutic efficacy of Listeriaat‐Mage‐b vaccine in correlation with improved T‐cell responses in blood of a triple‐negative breast cancer model 4T1

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Curcumin improves the therapeutic efficacy of Listeria^at‐Mage‐b vaccine in correlation with improved T‐cell responses in blood of a triple‐negative breast cancer model 4T1