Intratumoral Administration of Recombinant Murine Interleukin‐12 Prevents Tumor Progression and Bone Invasion

Abstract

ABSTRACT Background Oral squamous cell carcinoma (OSCC) progression is accompanied by bone invasion. Therefore, maintaining oral function is necessary to regulate tumor progression. Also, interleukin-12 (IL-12), a well-known anti-tumor cytokine, can suppress osteoclast differentiation in vitro. Accordingly, this study evaluated the therapeutic effects of locally administered IL-12 in an immunocompetent mouse model with mandibular bone invasion mimicking clinical features. Methods We investigated anti-bone resorption effects using SCCVII subcutaneous and bone invasion models both in immunocompetent and athymic mice. Furthermore, we measured bone resorption using micro-computed tomography. Results Intratumoral injection of recombinant murine IL-12 (r-mIL-12) significantly prolonged immunocompetent mouse survival and suppressed tumor growth and bone resorption. Real-time PCR analysis revealed that interferon-gamma (IFN-γ) and Fas ligand (FasL) were upregulated after r-mIL-12 administration, compared to control levels. However, when the athymic mouse bone invasion model was evaluated, r-mIL-12-mediated suppression of tumor growth and bone resorption were equivalent to those observed in the control group, highlighting the key role of T cells in the bone invasion. Conclusions r-mIL-12 may represent a potent therapeutic agent for OSCC accompanied by bone invasion. SUMMARY Intratumoral injection of recombinant murine IL-12 showed anti-tumor and anti-bone resorption effects in an immunocompetent mouse bone invasion model through a T cell-dependent mechanism.