IL-17RC is associated with improved survival and modulates tumor cell phenotypes in oral squamous cell carcinoma

Oral squamous cell carcinoma (OSCC) exhibits marked biological heterogeneity, resulting in variable clinical outcomes and limited therapeutic response. Recent evidence has highlighted the involvement of interleukin-17 family cytokines in several cancer types. However, the role of the interleukin-17 receptor C (IL-17RC) in OSCC remains unexplored. Therefore, this study aimed to investigate the prognostic value and biological role of IL-17RC in OSCC.
A retrospective immunohistochemical analysis was performed on 235 OSCC specimens, correlating IL-17RC expression with clinicopathological parameters and patient survival. Functional analyses were conducted using two OSCC cell lines (HSC3 and SCC25) subjected to IL-17RC knockdown, followed by assays evaluating cell viability, proliferation, migration, invasion, and response to radiation. In addition, immune cell migration toward cancer cells was assessed using a microfluidic chip.
High IL-17RC expression was associated with clinicopathological features related to tumor behavior and emerged as an independent predictor of improved disease-specific survival and disease-free survival. In vitro, IL-17RC knockdown in HSC3 cells increased proliferation and reduced immune cell recruitment. In SCC25 cells, IL-17RC depletion decreased migration and invasion. In both cell lines, IL-17RC knockdown reduced post-irradiation cell viability.
These findings indicate that elevated IL-17RC expression is independently associated with favorable clinical outcomes, supporting its potential as a prognostic biomarker in OSCC. Furthermore, the distinct in vitro effects observed across cell lines suggest that IL-17RC may differentially regulate pathways involved in proliferation, invasion, cell survival, and cancer–immune cell crosstalk. These observations may reflect the biological heterogeneity of OSCC and underscore the need for further investigation of IL-17RC within the tumor microenvironment.