Microwave ablation combined with dendritic cells enhances CD8+ T cell activation in rechallenged tumor mouse model
摘要
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.
MethodsA 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.
ResultsThe 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.
ConclusionOur 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.