Macrophage hitchhiking for systematic suppression in postablative multifocal HCC.

Area of Science:

• Oncology
• Biomedical Engineering
• Immunotherapy

Background:

• Multifocal hepatocellular carcinoma (HCC) presents aggressive invasion and poor prognosis.
• Locoregional treatments often fail to eliminate residual tumor cells, leading to progression.
• Systemic therapies like lenvatinib (LEN) have limited efficacy due to poor tumor tissue delivery.

Purpose of the Study:

• To develop an advanced strategy for postablative multifocal HCC therapy.
• To enhance the delivery efficiency of systemic therapies to residual tumor cells.
• To improve clinical outcomes for patients with multifocal HCC.

Main Methods:

• A microinvasive ablation-guided macrophage hitchhiking strategy was developed.
• Lenvaltinib (LEN)-loaded macrophages were guided by the inflammatory gradient induced by ablation.
• The strategy was tested in multifocal HCC mouse and rabbit models.

Main Results:

• Macrophage hitchhiking increased LEN delivery efficiency by approximately 10-fold in vivo.
• The strategy demonstrated significant antitumor activity, inhibiting residual tumor progression.
• Enhanced LEN delivery stimulated systemic immune responses and induced durable immune memory, prolonging median survival.

Conclusions:

• The macrophage hitchhiking strategy shows high therapeutic efficacy and biosafety across species.
• This approach offers promising prospects for clinical translation in controlling HCC progression post-ablation.
• The strategy holds potential for improving patient outcomes following HCC ablation.