Melanoma-associated antigen genes: a new trend to predict the prognosis of breast cancer patients

Abdelsalam, Eman; Ismaeil, Nadia A.

doi:10.1007/s12032-014-0285-0

Cited by 15 publications

(8 citation statements)

References 15 publications

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“…Aberrant over-expression of MAGEA12 has been identified in oral squamous cell carcinoma and breast cancer [14,15]. Interestingly, MAGEA12 mRNA can be detected in the blood of 13% breast cancers, and may be used as a biomarker to monitor the progression and therapeutic effectiveness [15]. In this study, we further identified MAGEA12 expression as a novel predictor for the outcome of gastric cancers.…”

Section: Discussionmentioning

confidence: 62%

“…Yamada et al [13] found that MAGEA12 showed high expression in cancer stem cells, a subgroup with a typical outlier distribution within tumors. Aberrant over-expression of MAGEA12 has been identified in oral squamous cell carcinoma and breast cancer [14,15]. Interestingly, MAGEA12 mRNA can be detected in the blood of 13% breast cancers, and may be used as a biomarker to monitor the progression and therapeutic effectiveness [15].…”

Section: Discussionmentioning

confidence: 99%

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Identification of MAGEA12 as a prognostic outlier gene in gastric cancers

Wu¹,

Wang²,

Shen³

2017

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Melanoma antigen (MAGE) family genes are frequently over-expressed in a subset population of multiple cancers, and serve as idea therapeutic targets; however, their distribution pattern in gastric cancers has not yet been evaluated. In this study, we first performed a cancer outlier profile analysis (COPA) on a series of public gene expression datasets of gastric cancer, and identified MAGEA12 showing a significant outlier expression model reproducibly. We further in silico validated that MAGEA12 outlier over-expression were associated with poor clinical outcome using six microarray datasets from GEO database. We then experimentally detected the MAGEA12 expression in an independent cohort of gastric cancer samples by immunohistochemistry, and showed that over-expression of MAGEA12 in a subset of cancers was associated with later stage and reduced survival; furthermore, MAGEA12 was an independent prognostic factor in an outlier manner. Our results indicate that MAGEA12 is a novel prognostic outlier gene in gastric cancers and patterns of MAGE expression may inform individualized targeted immunotherapies.

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Section: Discussionmentioning

confidence: 62%

Section: Discussionmentioning

confidence: 99%

Identification of MAGEA12 as a prognostic outlier gene in gastric cancers

Wu¹,

Wang²,

Shen³

2017

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“…Furthermore, the observation of ELIspot response to MAGE-A1 in breast cancer is intriguing since there are recently reports of immunogenicity of MAGE-A1 for breast cancer patients [ 57 – 60 ]. It was previously reported that 27% of breast tumors are positive for at least one of the MAGE transcripts and MAGE expression was more common in ductal breast cancer and Ki-67 high tumors [ 61 ].…”

Section: Discussionmentioning

confidence: 99%

A pilot study of the immunogenicity of a 9-peptide breast cancer vaccine plus poly-ICLC in early stage breast cancer

Dillon

Petroni

Smolkin

et al. 2017

j. immunotherapy cancer

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BackgroundBreast cancer remains a leading cause of cancer death worldwide. There is evidence that immunotherapy may play a role in the eradication of residual disease. Peptide vaccines for immunotherapy are capable of durable immune memory, but vaccines alone have shown sparse clinical activity against breast cancer to date. Toll-like receptor (TLR) agonists and helper peptides are excellent adjuvants for vaccine immunotherapy and they are examined in this human clinical trial.MethodsA vaccine consisting of 9 MHC class I-restricted breast cancer-associated peptides (from MAGE-A1, −A3, and -A10, CEA, NY-ESO-1, and HER2 proteins) was combined with a TLR3 agonist, poly-ICLC, along with a helper peptide derived from tetanus toxoid. The vaccine was administered on days 1, 8, 15, 36, 57, 78. CD8+ T cell responses to the vaccine were assessed by both direct and stimulated interferon gamma ELIspot assays.ResultsTwelve patients with breast cancer were treated: five had estrogen receptor positive disease and five were HER2 amplified. There were no dose-limiting toxicities. Toxicities were limited to Grade 1 and Grade 2 and included mild injection site reactions and flu-like symptoms, which occurred in most patients. The most common toxicities were injection site reaction/induration and fatigue, which were experienced by 100% and 92% of participants, respectively. In the stimulated ELIspot assays, peptide-specific CD8+ T cell responses were detected in 4 of 11 evaluable patients. Two patients had borderline immune responses to the vaccine. The two peptides derived from CEA were immunogenic. No difference in immune response was evident between patients receiving endocrine therapy and those not receiving endocrine therapy during the vaccine series.ConclusionsPeptide vaccine administered in the adjuvant breast cancer setting was safe and feasible. The TLR3 adjuvant, poly-ICLC, plus helper peptide mixture provided modest immune stimulation. Further optimization is required for this multi-peptide vaccine/adjuvant combination.Trial registration ClinicalTrials.gov (posted 2/15/2012): NCT01532960. Registered 2/8/2012. https://clinicaltrials.gov/show/NCT01532960 Electronic supplementary materialThe online version of this article (10.1186/s40425-017-0295-5) contains supplementary material, which is available to authorized users.

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“…Next to these mutation-specific neoantigens, other tumor-associated antigens (TAA) are autoantigens which are expressed excessively, differentiation-specific antigens, cancer testis genes (CTA) that display normal expression in immune-privileged organs but aberrant expression in several types of cancer including BC-modified autoantigens, TAA that are highly expressed in tumors such as HER2/neu, and viral-associated antigens. For example, members of the CTA family of melanoma-associated antigens (MAGEs), MAGE-A9 and MAGE-A11, are less expressed in estrogen receptor(ER)-negative and HER2/neu-negative BC [13,14]. In contrast, upregulation of MAGE-A9 in invasive ductal BC is correlated with an unfavorable outcome for patients [15].…”

Section: Breast Cancer and Tumor-associated Antigensmentioning

confidence: 99%

The Role of Immune Escape and Immune Cell Infiltration in Breast Cancer

2018

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While detailed analysis of aberrant cancer cell signaling pathways and changes in cancer cell DNA has dominated the field of breast cancer biology for years, there now exists increasing evidence that the tumor microenvironment (TME) including tumor-infiltrating immune cells support the growth and development of breast cancer and further facilitate invasion and metastasis formation as well as sensitivity to drug therapy. Furthermore, breast cancer cells have developed different strategies to escape surveillance from the adaptive and innate immune system. These include loss of expression of immunostimulatory molecules, gain of expression of immunoinhibitory molecules such as PD-L1 and HLA-G, and altered expression of components involved in apoptosis. Furthermore, the composition of the TME plays a key role in breast cancer development and treatment response. In this review we will focus on i) the different immune evasion mechanisms used by breast cancer cells, ii) the role of immune cell infiltration in this disease, and (iii) implication for breast cancer-based immunotherapies.

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Melanoma-associated antigen genes: a new trend to predict the prognosis of breast cancer patients

Cited by 15 publications

References 15 publications

Identification of MAGEA12 as a prognostic outlier gene in gastric cancers

Identification of MAGEA12 as a prognostic outlier gene in gastric cancers

A pilot study of the immunogenicity of a 9-peptide breast cancer vaccine plus poly-ICLC in early stage breast cancer

The Role of Immune Escape and Immune Cell Infiltration in Breast Cancer

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