Enhanced antitumor efficacy through microwave ablation in combination with immune checkpoints blockade in breast cancer: A pre-clinical study in a murine model.

Abstract

The purpose of this study was to investigate the therapeutic efficacy of the combination of microwave ablation (MWA) in combination with immune checkpoints blockade in the treatment of breast cancer using the 4T1 tumor-bearing mice model. We treated tumor-bearing mice with MWA, programmed cell death protein1 (PD-1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) blockade (P+C), MWA plus PD-1 and CTLA-4 blockade (combination therapy), or no-treatment. Survival time was evaluated with the Kaplan-Meyer method comparing survival curves by log-rank test. On day 15 after MWA, five mice from the combination therapy group received tumor rechallenge with 4T1 or CT26 cells and the volumes of rechallenge tumor were calculated every 5 days. Immune cells were identified by immunohistochemistry and flow cytometry, and the concentrations of plasma interferon-γ (IFN-γ) were identified by enzyme-linked immunosorbent assay (ELISA). The combination therapy significantly prolonged tumor-bearing mice survival compared to no-treatment group, P+C group or MWA group (P<0.001, P<0.001 and P=0.01, respectively) and protected most surviving mice from 4T1 tumor rechallenge (P=0.002) but not CT26 tumor rechallenge (P=0.905). Both local and systemic CD8+ T-cell responses were induced by MWA (all P<0.05) and further augmented by subsequent administration of PD-1 and CTLA-4 blockade (all P<0.05). Plasma IFN-γ concentrations were significantly elevated in the combination therapy group compared to no-treatment group, P+C group or MWA group (P<0.001, P<0.001 and P=0.01, respectively). MWA combined with immune checkpoints blockade could synergistically enhance antitumor efficacy with augmented specific immune responses, and the combination therapy is a promising approach to treat breast cancer.