Investigation of the CTLA-4–CD28 Axis in Oral Squamous Cell Carcinoma

Feldmeier F, Weber M, Pacelli F, Vogl C, Glajzer J, Trumet L, Buchbender M, Geppert CI, Kesting MR, Ries J (2025)

Publication Type: Journal article

Publication year: 2025

Journal

Journal of Clinical Medicine MDPI

Book Volume: 14

Article Number: 5171

Journal Issue: 14

DOI: 10.3390/jcm14145171

Abstract

Background: Oral squamous cell carcinoma (OSCC) is a common head and neck cancer with low survival rates, especially in advanced stages, despite improved therapies. New developments show that immune checkpoint inhibitors (ICIs) are promising treatment options. A better understanding of immune suppression in OSCC could enable new therapeutic approaches and effective ICI combinations. Methods: The aim of this cross-sectional study was to investigate the significance of the differential expression of cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), CD28 and their ligands CD80 and CD86 for the diagnosis and treatment of OSCC. To this end, mRNA expression was analysed by RT-PCR and compared in 65 healthy oral mucosa samples (NOM) and 104 OSCC samples. Results: The expression of CTLA-4 (a soluble and membrane-bound isoform) was increased in OSCC by 1.72-fold (p = 0.004) and 6.88-fold (p < 0.001), respectively. There was no significant difference for CD28 (p = 0.283), nor for the soluble isoform of CD86 (p = 0.845). The membrane isoform of CD86 was increased in OSCC by a factor of 1.39 (p = 0.009) and CD80 by 6.11-fold (p < 0.001). Conclusions: The results show a significant association between CTLA-4, CD80 and membrane-bound CD86 expression and diagnosis. They could improve diagnostics in multi-marker approaches and serve as therapeutic targets for ICI strategies. In particular, the data indicate a stronger immunosuppressive role of CD80 compared to CD86 in a tumor tissue context, suggesting the exploration of anti-CTLA-4 and anti-CD80 antibody combinations in animal models.

Authors with CRIS profile

Manuel Weber Department of Oral and Cranio-Maxillofacial Surgery Christoph Vogl Department of Oral and Cranio-Maxillofacial Surgery Jacek Glajzer Department of Oral and Cranio-Maxillofacial Surgery Leah Trumet Department of Operative Dentistry and Periodontology Mayte Buchbender Department of Oral and Cranio-Maxillofacial Surgery Carol-Immanuel Geppert Institute of Pathology Marco Rainer Kesting Lehrstuhl für Zahnmedizin, insbesondere Mund-, Kiefer-, und Gesichtschirurgie (MKG) Jutta Ries Department of Oral and Cranio-Maxillofacial Surgery

How to cite

APA:

Feldmeier, F., Weber, M., Pacelli, F., Vogl, C., Glajzer, J., Trumet, L.,... Ries, J. (2025). Investigation of the CTLA-4–CD28 Axis in Oral Squamous Cell Carcinoma. Journal of Clinical Medicine, 14(14). https://doi.org/10.3390/jcm14145171

MLA:

Feldmeier, Ferdinand, et al. "Investigation of the CTLA-4–CD28 Axis in Oral Squamous Cell Carcinoma." Journal of Clinical Medicine 14.14 (2025).

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