Preclinical study of TLR stimulation combined PD-1 antibody enhance the therapeutic effect of microwave ablation on NSCLC

The purpose of this study was to investigate the therapeutic efficacy of the combination of microwave ablation (MWA) with immune checkpoints blockade and TLR9 stimulation in the treatment of non-small cell lung cancer (NSCLC) using the C57BL/6 tumor-bearing mice model.

Tumor-bearing mice were treated with MWA, programmed cell death protein1 blockade (PD-1) plus MWA (MWA + P), TLR9 agonist CpG ODNs and MWA (MWA + C), PD-1 blockade and CpG ODNs (P + C), MWA plus PD-1 blockade and CpG ODNs (MWA + P + C), or untreated. Survival time was evaluated with the Kaplan–Meyer method comparing survival curves by log-rank test. On day 15 after MWA, ten mice from the combination therapy group received tumor rechallenge with LLC 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 IFN-γ、TNF-α and TGF-β were identified by enzyme-linked immunosorbent assay (ELISA).

The MWA + P + C combination therapy significantly prolonged tumor-bearing mice survival and reduced tumor size compared to untreated group, MWA group, MWA + P group, M + C group, P + C group. The combination therapy also protected most surviving mice from LLC tumor rechallenge. CD8 + T-cell in tumor and spleen were remarkably induced by MWA + P + C and Treg cell further diminished by combination therapy. Both tumor necrosis factor-alpha (TNF-α) and interferon-gama (IFN-γ) concentrations in plasma were significantly elevated in the combination therapy group compared to other groups, while transforming growth factor Beta (TGF-β) was reduced.

MWA combined with immune checkpoints blockade and TLR stimulation could significantly enhance antitumor efficacy with augmented specific immune responses, and the combination therapy is a promising approach to treat non-small cell lung cancer (NSCLC).