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Volume 27
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10.3390/ijms27115069
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This is an early access version, the complete PDF, HTML, and XML versions will be available soon.
Article

Last Licensed Non-Classical Peptide Presenter HLA-F: Its Occurrence, Immunoediting Significance, and Possible Therapeutic Implications in Renal Cell Carcinoma

by
Libuše Janků
1,2,
Michal Fedorko
3,
Marek Kašík
3,
Táňa Macháčková
4 and
Leoš Křen
5,6,*
1
Transfusion and Tissue Department, University Hospital Brno, 625 00 Brno, Czech Republic
2
Department of Laboratory Medicine, Faculty of Medicine, Masaryk University, 625 00 Brno, Czech Republic
3
Department of Urology, University Hospital Brno, Faculty of Medicine, Masaryk University, Brno, Czech Republic
4
Department of Biology, Faculty of Medicine and CEITEC, Masaryk University, 625 00 Brno, Czech Republic
5
Department of Pathology, Faculty of Medicine, Masaryk University, 625 00 Brno, Czech Republic
6
Department of Pathology, University Hospital Brno, 625 00 Brno, Czech Republic
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2026, 27(11), 5069; https://doi.org/10.3390/ijms27115069
Submission received: 15 April 2026 / Revised: 28 May 2026 / Accepted: 29 May 2026 / Published: 3 June 2026
(This article belongs to the Special Issue Advanced Research on the Major Histocompatibility Complex (MHC): From Bench to Bedside)
Versions Notes

Abstract

Among non-classical human leukocyte antigen (HLA) molecules, HLA-F remains the most enigmatic. Its precise functions, including the recently described peptide-presenting capability, are still not fully understood. Renal cell carcinoma (RCC) is characterized by its resistance to radiotherapy and chemotherapy, and it is known for its immunogenicity. The prognostic significance of HLA-F expression in neoplastic cells has not been well defined. We evaluated HLA-F–specific mRNA transcripts in 73 RCC samples and 54 adjacent normal kidney parenchyma samples and statistically correlated the results with several clinicopathological parameters. Our analysis revealed that HLA-F is upregulated in RCC. Interestingly, higher HLA-F expression was associated with prolonged disease-free survival, more favorable pT stage, and lower WHO/ISUP grade. Given the potential for interferon-mediated aberrant activation of non-classical HLA molecules, assessment of HLA-F status could help identify RCC patients who might benefit from tailored neoadjuvant biological or immunological therapies. Overall, HLA-F may serve as a valuable prognostic biomarker in RCC, and further studies are warranted to elucidate its functional and clinical significance.
Keywords: HLA-F; renal cell carcinoma; non-classical HLA molecules HLA-F; renal cell carcinoma; non-classical HLA molecules

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MDPI and ACS Style

Janků, L.; Fedorko, M.; Kašík, M.; Macháčková, T.; Křen, L. Last Licensed Non-Classical Peptide Presenter HLA-F: Its Occurrence, Immunoediting Significance, and Possible Therapeutic Implications in Renal Cell Carcinoma. Int. J. Mol. Sci. 2026, 27, 5069. https://doi.org/10.3390/ijms27115069

AMA Style

Janků L, Fedorko M, Kašík M, Macháčková T, Křen L. Last Licensed Non-Classical Peptide Presenter HLA-F: Its Occurrence, Immunoediting Significance, and Possible Therapeutic Implications in Renal Cell Carcinoma. International Journal of Molecular Sciences. 2026; 27(11):5069. https://doi.org/10.3390/ijms27115069

Chicago/Turabian Style

Janků, Libuše, Michal Fedorko, Marek Kašík, Táňa Macháčková, and Leoš Křen. 2026. "Last Licensed Non-Classical Peptide Presenter HLA-F: Its Occurrence, Immunoediting Significance, and Possible Therapeutic Implications in Renal Cell Carcinoma" International Journal of Molecular Sciences 27, no. 11: 5069. https://doi.org/10.3390/ijms27115069

APA Style

Janků, L., Fedorko, M., Kašík, M., Macháčková, T., & Křen, L. (2026). Last Licensed Non-Classical Peptide Presenter HLA-F: Its Occurrence, Immunoediting Significance, and Possible Therapeutic Implications in Renal Cell Carcinoma. International Journal of Molecular Sciences, 27(11), 5069. https://doi.org/10.3390/ijms27115069

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