# Mapping MAGE-A4 expression in solid cancers for targeted therapies

**Authors:** Christin Habigt, Sylvie Rottey, Iben Spanggaard, Juanita S. Lopez, Elena Garralda, Emiliano Calvo, Oliver Bechter, Jayesh Desai, Rachel Galot, Leena Gandhi, Florian Heil, Natascha Rieder, Ivan Dimitrov, Iris Martinez Quetglas, Christian Heichinger, Nino Keshelava, Andreas Roller

PMC · DOI: 10.3389/fonc.2025.1484182 · Frontiers in Oncology · 2025-03-13

## TL;DR

This study maps MAGE-A4 protein expression in various solid cancers to identify which cancers may benefit most from anti-MAGE-A4 therapies.

## Contribution

The study provides new insights into MAGE-A4 expression patterns across multiple cancer types, highlighting potential for targeted treatment strategies.

## Key findings

- MAGE-A4 was expressed in 35% of the overall patient cohort.
- Adenoid cystic carcinoma showed the highest MAGE-A4 positivity at 82%.
- The study identified significant variability in MAGE-A4 expression across different cancer types.

## Abstract

Melanoma-associated antigen A4 (MAGE-A4) is a promising target for anticancer therapy. However, limited contemporary data are available on the details of MAGE-A4 protein expression in different cancer types. In this study, the protein expression of MAGE-A4 is comprehensively studied in patients with unresectable and/or metastatic solid cancers to identify indications of the highest unmet medical need for anti-MAGE-A4 therapy. FFPE tumor sections from 200 patients, predominantly HLA-A*02:01 positive (n = 193), were examined using immunohistochemistry (IHC) to detect MAGE-A4 expression. The patient cohort comprised various cancer types to pinpoint differences in the prevalence and intensity of MAGE-A4 positivity. MAGE-A4 expression was observed in 35% (69 patients) of the overall cohort. Certain cancer types exhibited notably higher frequencies of MAGE-A4 positivity. Specifically, adenoid cystic carcinoma demonstrated the highest prevalence at 82%, followed by liposarcoma at 67%. Ovarian serous/high-grade carcinoma showed a 64% positivity rate, identical to that observed in squamous non-small cell lung cancer (NSCLC). Head and neck squamous cell carcinoma (HNSCC) presented a 60% prevalence, while esophageal cancer had a 54% prevalence of MAGE-A4 expression. These data highlight the variability of MAGE-A4 expression across different cancer types and underscore its relevance as a potential target of novel precision medicines. The significant presence of MAGE-A4 in specific cancers suggests potential for stratified therapeutic approaches and warrants further investigation into its role in oncogenesis and treatment response.

## Linked entities

- **Genes:** MAGEA4 (MAGE family member A4) [NCBI Gene 4103]
- **Diseases:** adenoid cystic carcinoma (MONDO:0004971), liposarcoma (MONDO:0003585), head and neck squamous cell carcinoma (MONDO:0010150), esophageal cancer (MONDO:0007576)

## Full-text entities

- **Genes:** MAGEA4 (MAGE family member A4) [NCBI Gene 4103] {aka CT1.4, MAGE-41, MAGE-X2, MAGE4, MAGE4A, MAGE4B}
- **Diseases:** HNSCC (MESH:D000077195), cancer (MESH:D009369), NSCLC (MESH:D002289), Ovarian serous/high-grade carcinoma (MESH:D010051), esophageal cancer (MESH:D004938), adenoid cystic carcinoma (MESH:D003528), liposarcoma (MESH:D008080)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

1 figure with captions in the complete paper: https://tomesphere.com/paper/PMC11947667/full.md

## References

16 references — full list in the complete paper: https://tomesphere.com/paper/PMC11947667/full.md

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Source: https://tomesphere.com/paper/PMC11947667