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bioRxiv · 10.1101/2023.05.26.542415

Intratumoral administration of recombinant murine interleukin-12 prevents tumor progression and bone invasion

Uchihashi, T.·Kasahara, S.·Inubushi, T.·Kurioka, K.·Sugauchi, A.·Miyagawa, K.·Kogo, M.·Tanaka, S.
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Abstract

BackgroundOral 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. MethodsWe 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. ResultsIntratumoral 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-{gamma}) 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. Conclusionsr-mIL-12 may represent a potent therapeutic agent for OSCC accompanied by bone invasion. SUMMARYIntratumoral 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.

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Uchihashi, T., Kasahara, S., Inubushi, T., Kurioka, K., Sugauchi, A., Miyagawa, K., Kogo, M., Tanaka, S.. 2023-05-27. Intratumoral administration of recombinant murine interleukin-12 prevents tumor progression and bone invasion. https://doi.org/10.1101/2023.05.26.542415

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