Microwave ablation combined with dendritic cells enhances CD8T cell activation in rechallenged tumor mouse model.

Abstract

OBJECTIVE: Microwave ablation (MWA) has shown favorable safety and efficacy in patients with non-small cell lung cancer (NSCLC). However, local recurrence remains a major concern that compromises long-term survival. Dysfunction of dendritic cells (DCs) constitutes a key immunosuppressive factor that limits effective T cell-mediated antitumor responses. To overcome this limitation, we evaluated the therapeutic potential of combining MWA with DC-based immunotherapy. METHODS: A Lewis lung carcinoma (LLC) rechallenge mouse model was established to assess the efficacy of the combination of MWA and DC therapy in preventing post-ablation tumor recurrence. The immune landscape in tumors and tumor-draining lymph nodes (TdLNs) was analyzed by flow cytometry. RESULTS: The combination of MWA and DC therapy markedly suppressed tumor recurrence and promoted potent antitumor immunity, as evidenced by an increased proportion and functional activation of CD8⁺ T cells in both recurrent tumors and TdLNs. In addition, the combination treatment substantially increased the frequency and immunostimulatory capacity of migratory type 1 conventional dendritic cells (Mig cDC1s) within TdLNs. These results indicate that cDC1s are crucial mediators of the enhanced antitumor response induced by MWA combined with DC therapy. CONCLUSION: Our findings highlight a synergistic antitumor mechanism of MWA and DC-based therapy through cDC1 activation and CD8⁺ T cell enhancement, providing a promising strategy to reduce tumor recurrence after MWA.