The protective role of IL-17C in oral squamous cell carcinoma

Zivile Giedraityte; Joosua Suominen; Wafa Wahbi; Ahana Kapuge Dona Varuni Yashodha Ratnayake; Tuulia Onali; Martina Giacomini; Sami Kilpinen; Katja Korelin; Maija Risteli; Tuula Salo; Ahmed Al-Samadi

doi:10.1016/j.tranon.2025.102541

The protective role of IL-17C in oral squamous cell carcinoma

Transl Oncol. 2025 Dec:62:102541. doi: 10.1016/j.tranon.2025.102541. Epub 2025 Sep 19.

Affiliations

¹ Department of Oral and Maxillofacial Diseases, Clinicum, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
² Institute of Dentistry, School of Medicine, Faculty of Health Sciences, University of Eastern Finland, Kuopio, Finland.
³ Department of Oral and Maxillofacial Diseases, Clinicum, Faculty of Medicine, University of Helsinki, Helsinki, Finland; Translational Immunology Research Programme (TRIMM), University of Helsinki, Helsinki, Finland.
⁴ Molecular and Integrative Biosciences Research Programme, Faculty of Biological and Environmental Sciences, University of Helsinki, Helsinki, Finland.
⁵ Research Unit of Population Health, Faculty of Medicine, University of Oulu, Oulu, Finland; Medical Research Centre, Oulu University Hospital, University of Oulu, Oulu, Finland.
⁶ Department of Oral and Maxillofacial Diseases, Clinicum, Faculty of Medicine, University of Helsinki, Helsinki, Finland; Translational Immunology Research Programme (TRIMM), University of Helsinki, Helsinki, Finland; Research Unit of Population Health, Faculty of Medicine, University of Oulu, Oulu, Finland; Medical Research Centre, Oulu University Hospital, University of Oulu, Oulu, Finland; Department of Pathology, HUSLAB, Helsinki University Central Hospital, University of Helsinki, Helsinki, Finland.
⁷ Department of Oral and Maxillofacial Diseases, Clinicum, Faculty of Medicine, University of Helsinki, Helsinki, Finland; Institute of Dentistry, School of Medicine, Faculty of Health Sciences, University of Eastern Finland, Kuopio, Finland; iCAN Digital Precision Cancer Medicine Flagship, University of Helsinki, Helsinki, Finland. Electronic address: ahmed.al-samadi@helsinki.fi.

Abstract

Background: Oral squamous cell carcinoma (OSCC) is a common cancer characterised by high rates of metastasis and mortality. Interleukin‑17C (IL-17C) is expressed by several cell types, including epithelial cells, and signals through the heterodimeric IL-17RE/IL-17RA receptor complex at various mucosal sites. The role of IL-17C in OSCC development and progression remains unexamined; therefore, this study aimed to elucidate its potential involvement.

Methods: Among 11 OSCC cell lines, OU-OTSCC-7B and UH-SCC-17B exhibited a high transcript expression of IL-17C receptors (IL-17RE and IL-17RA) and were selected for further assays. Proliferation, apoptosis, migration, and invasion assays were conducted in the presence and absence of IL-17C. Using a zebrafish xenograft model, we assessed the in vivo effects of IL-17C. Additionally, we performed RNA sequencing after stimulating UH-SCC-17B cells with IL-17C.

Results: IL-17C significantly inhibited the proliferation and migration of UH-SCC-17B cells, but had no effect on OU-OTSCC-7B cells. Moreover, IL-17C reduced the tumour size of UH-SCC-17B cells by approximately 10% in the zebrafish model. RNA sequencing revealed the downregulation of five genes, three of which were mitochondrial genes-MT-CYB, MT-ND1, and MTND2P28-implicated in cancer progression. Gene set enrichment analysis revealed the enrichment of the MYC target and oxidative phosphorylation gene sets following IL-17C treatment.

Conclusions: IL-17C appears to play a protective role in some OSCC cells. While this study indicates the potential of using IL-17C as a therapeutic candidate for OSCC patients, its relatively mild and selective effect suggests it may be more effective as part of a combination therapy.

Keywords: Cytokine; IL-17C; Oral cancer; Proliferation; Zebrafish.