Targeting the MAGE A3 antigen in pancreatic cancer

Cogdill, Alexandria P.; Frederick, Dennie T.; Cooper, Zachary A.; Garber, Haven R.; Ferrone, Cristina R.; Fiedler, Amy G.; Rosenberg, Laura M.; Thayer, Sarah P.; Warshaw, Andrew L.; Wargo, Jennifer A.

doi:10.1016/j.surg.2012.05.031

Cited by 18 publications

(14 citation statements)

References 24 publications

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“…CTAs have already been analyzed in different types of malignancies, including carcinomas of the liver, pancreas, bladder and the breast . CTA expression in lung cancer, medullary breast and urothelial carcinoma has also been found to impact patients' OS …”

Section: Discussionmentioning

confidence: 99%

Simultaneous cytoplasmic and nuclear protein expression of melanoma antigen‐A family and NY‐ESO‐1 cancer‐testis antigens represents an independent marker for poor survival in head and neck cancer

Laban

Atanackovic

Luetkens

et al. 2014

Intl Journal of Cancer

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The prognosis of head and neck squamous cell carcinoma (HNSCC) patients remains poor. The identification of high-risk subgroups is needed for the development of custom-tailored therapies. The expression of cancer-testis antigens (CTAs) has been linked to a worse prognosis in other cancer types; however, their prognostic value in HNSCC is unclear because only few patients have been examined and data on CTA protein expression are sparse. A tissue microarray consisting of tumor samples from 453 HNSCC patients was evaluated for the expression of CTA proteins using immunohistochemistry. Frequency of expression and the subcellular expression pattern (nuclear, cytoplasmic, or both) was recorded. Protein expression of melanoma antigen (MAGE)-A family CTA, MAGE-C family CTA and NY-ESO-1 was found in approximately 30, 7 and 4% of tumors, respectively. The subcellular expression pattern in particular had a marked impact on the patients' prognosis. Median overall survival (OS) of patients with (i) simultaneous cytoplasmic and nuclear expression compared to (ii) either cytoplasmic or nuclear expression and (iii) negative patients was 23.0 versus 109.0 versus 102.5 months, for pan-MAGE (p < 0.0001), 46.6 versus 50.0 versus 109.0 for MAGE-A3/A4 (p 5 0.0074) and 13.3 versus 50.0 versus 100.2 months for NY-ESO-1 (p 5 0.0019). By multivariate analysis, these factors were confirmed as independent markers for poor survival. HNSCC patients showing protein expression of MAGE-A family members or NY-ESO-1 represent a subgroup with an extraordinarily poor survival. The development of immunotherapeutic strategies targeting these CTA may, therefore, be a promising approach to improve the outcome of HNSCC patients.

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Section: Discussionmentioning

confidence: 99%

Simultaneous cytoplasmic and nuclear protein expression of melanoma antigen‐A family and NY‐ESO‐1 cancer‐testis antigens represents an independent marker for poor survival in head and neck cancer

Laban

Atanackovic

Luetkens

et al. 2014

Intl Journal of Cancer

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“…In these studies, treatment with decitabine or azacitidine exhibit a response rate up to 30% that was relatively durable when compared to placebo [96,97]. Azacitidine is now also being evaluated in clinical trials on other malignant diseases such as non-small cell lung cancer and pancreatic cancer [98,99]. …”

Section: Introductionmentioning

confidence: 99%

Epigenetic changes: a common theme in acute myelogenous leukemogenesis

Gutiérrez

Romero-Oliva

2013

J Hematol Oncol

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Acute myeloid leukemia (AML) is a rather common disease, characterized by the presence of a clonal population of hematopoietic progenitor cells with impaired differentiation. Although traditionally AML has been considered the result of genetic alterations, more recently experimental evidence have demonstrated that epigenetic modifications are important in development and maintenance of leukemia cells. In this review we summarize current scientific knowledge of epigenetic alterations involved in leukemogenesis. We also highlight the developing of new technological strategies that are based on epigenetic processes and have been registered as Patents of Inventions in the United Nations dependent World Intellectual Property Office (WIPO) and the main Patent offices worldwide.

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“…Like other HDACi agents, a large body of evidence indicates that TSA has the potential to enhance the recognition of neoplastic cells by immune cells, especially by inducing the expression of specific TAAs. In particular, TSA induces MAGE‐A3 expression in pancreatic cancer cell lines, enhancing their recognition by MAGE‐A3–specific T‐cell lymphocytes . TSA also induces L antigen family member 1 (LAGE‐1) expression in KYSE150, KYSE960, and SKGT4 esophageal cancer cell lines; it enhances DAC‐induced expression of MAGE‐C2 in breast cancer cells, GAGE in SK‐Mel‐023 melanoma, centrin 1 (CETN1) in prostate cancer, and MAGE‐A1, MAGE‐A2, MAGE‐A3, and MAGE‐A12 in multiple cancer cell lines .…”

Section: Natural Compounds Possessing Epigenetic Properties That Stimmentioning

confidence: 99%

Anticancer potential of naturally occurring immunoepigenetic modulators: A promising avenue?

Schnekenburger

Dicato

Diederich

2019

Cancer

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The immune system represents the major primary defense line against carcinogenesis and acts by identifying and eradicating nascent transformed cells. A growing body of evidence is indicating that aberrant epigenetic reprogramming plays a key role in tumor immune escape through: 1) impaired efficient recognition of neoplastic cells by the immune system, resulting from a downregulation or loss of the expression of tumor‐associated antigens, human leukocyte antigens, antigen processing and presenting machinery, and costimulatory molecule genes; 2) aberrant expression of immune checkpoint proteins and their ligands; and 3) modification of cytokine profiles and tumor‐associated immune cell populations toward an immunosuppressive state in the tumor microenvironment. Consistent with the inherent reversibility of epigenetic alterations, epigenetic drugs, including DNA methyltransferase and histone deacetylase inhibitors, have the unique potential to favorably modify the tumor microenvironment, restore tumor recognition and stimulate an antitumor immune response. The objective of this review is to highlight selected, naturally occurring epigenetic modulators, namely, butyrate, curcumin, (−)‐epigallocatechin‐3‐gallate, resveratrol, romidepsin, and trichostatin A, with a special focus on their antitumor immune properties.

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Targeting the MAGE A3 antigen in pancreatic cancer

Cited by 18 publications

References 24 publications

Simultaneous cytoplasmic and nuclear protein expression of melanoma antigen‐A family and NY‐ESO‐1 cancer‐testis antigens represents an independent marker for poor survival in head and neck cancer

Simultaneous cytoplasmic and nuclear protein expression of melanoma antigen‐A family and NY‐ESO‐1 cancer‐testis antigens represents an independent marker for poor survival in head and neck cancer

Epigenetic changes: a common theme in acute myelogenous leukemogenesis

Anticancer potential of naturally occurring immunoepigenetic modulators: A promising avenue?

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