Microwave ablation combined with immune checkpoint inhibitor enhanced the antitumor immune activation and memory in rechallenged tumor mouse model.

Abstract

Microwave ablation (MWA) is a super minimally invasive therapeutic approach that has been widely applied in the treatment of non-small cell lung cancer (NSCLC). Although MWA can elicit antitumor immune responses, these immune responses are not relatively steady and insufficient to completely clear recurrence tumor cells within the body. Immunotherapy monotherapy has shown low clinical efficacy in the treatment of advanced NSCLC. MWA combined with immune checkpoint inhibitors (ICIs) is a promising therapeutic approach. However, the mechanism of synergic effect remains elusive. In this study, we have conducted a retrospective analysis of the clinical outcomes of MWA combined with ICIs, finding that the combinational therapy yielded superior Objective Response Rate and longer Progression-Free Survival. In preclinical models, we established a tumor rechallenged model to address post-MWA recurrence and to delve into the underlying mechanisms of the combined therapy. We observed that the combined treatment (MWA + PD-L1 blockade therapy) effectively addressed the issue of tumor recurrence in tumor rechallenged model. The combinational therapy increased the function and percentage of CD8⁺ tumor-infiltrating lymphocytes, enhanced the functionality of CD8⁺ T cells within tumor-draining lymph nodes (TdLNs), and elevated the proportion of T central memory cells. Additionally, the combined treatments promoted the proportion of Migration Dendritic Cells type 1 (Mig DC1) within TdLNs, thereby enhancing their activation potential. Notably, FTY720-mediated blockade of lymphocyte egress abolished the therapeutic benefits, confirming TdLNs-dependent systemic immunity. Moreover, the efficacy of the combinational therapy depended on the migration of T cells from TdLNs to tumor site. In summary, we proposed a potentially effective combined treatment regimen and have elucidated the underlying cellular mechanisms that underpin its efficacy.