IL-18 derived from microwave-ablated osteosarcoma facilitates antitumor response

Area of Science:

• Immunology
• Oncology
• Biomedical Engineering

Background:

• Osteosarcoma (OSA) is a primary bone cancer in children with stagnant survival rates.
• Microwave ablation (MWA) is an emerging thermal therapy for bone tumors.
• MWA's mechanism for inducing antitumor immunity, particularly its role in interleukin-18 (IL-18) expression and dendritic cell (DC) function, requires elucidation.

Purpose of the Study:

• To investigate the intrinsic mechanisms by which MWA induces antitumor immunity in osteosarcoma.
• To explore the role of IL-18 in MWA-mediated immune activation.
• To evaluate the therapeutic potential of combining IL-18 with anti-programmed cell death protein 1 (PD-1) therapy for osteosarcoma.

Main Methods:

• In vitro co-culture of MWA-treated osteosarcoma with bone marrow-derived dendritic cells (BMDCs).
• RNA sequencing to analyze molecular changes in BMDCs stimulated by MWA-treated osteosarcoma.
• In vivo mouse models of osteosarcoma to assess immune responses and therapeutic efficacy of IL-18 and anti-PD-1 combination therapy.

Main Results:

• MWA treatment enhanced BMDC activation, antigen uptake, and cross-presentation.
• MWA increased CD8+ T cell and CD11c+ DC infiltration in tumors and draining lymph nodes.
• Tumor suppression was IL-18 dependent, mediated by IL-18 release from MWA-treated osteosarcoma and interaction with IL-18 receptors on DCs; combination therapy showed additive effects.

Conclusions:

• IL-18-mediated signaling plays a critical role in MWA-induced protective immune responses against osteosarcoma.
• This study provides a novel mechanism for MWA-induced immune activation.
• IL-18 cytokine therapy represents a feasible and effective potential treatment approach for osteosarcoma.