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

Objective

Oral squamous cell carcinoma (OSCC) frequently invades the mandibular bone, leading to metastasis and poor prognosis. This study aimed to evaluate the therapeutic effects of locally administered interleukin-12 (IL-12) using an immunocompetent mouse model mimicking the clinical features of mandibular bone invasion.

Methods

The effects of IL-12 on tumor growth and bone resorption were evaluated using subcutaneous and bone invasion models of OSCC in both immunocompetent and athymic mice. Bone resorption was assessed by micro-computed tomography (CT). In addition, quantitative polymerase chain reaction (qPCR) was performed to quantify the expression of osteoclast markers (Acp5, Ctsk) and immune-related genes (Ifng, Fasl).

Results

Intratumoral injection of recombinant murine IL-12 (r-mIL-12) significantly prolonged mouse survival and suppressed tumor growth in immunocompetent mice. Micro-CT revealed reduced bone resorption in the r-mIL-12-treated group. Consistently, qPCR demonstrated downregulation of Acp5 and Ctsk, along with upregulation of Ifng and Fasl compared to controls. In contrast, r-mIL-12 treatment had no significant effect on tumor growth or bone resorption in athymic mice, underscoring the importance of T cells in controlling bone invasion.

Conclusions

These findings suggest that local administration of r-mIL-12 may serve as an effective therapeutic approach for OSCC with mandibular bone invasion.