Abstract
BackgroundMinimally invasive therapies, such as microwave ablation (MWA), are widely used for the treatment of solid tumors. Previous studies suggest that MWA is feasible for the treatment of small breast cancer, and thermal ablation may induce adaptive antitumor immunity. However, the induced immune responses are mostly weak, and the immunomodulation effects of MWA in breast cancer are unclear. Immunostimulant OK-432 can induce tumor-specific T-cell responses and may augment the immunity induced by MWA.MethodsWe treated 4T1 breast cancer bearing BALB/c mice with MWA, OK-432, MWA plus OK-432, or left without treatment. Survival time was evaluated with the Kaplan–Meyer method comparing survival curves by log-rank test. On day 25 after ablation, surviving mice received tumor rechallenge, and the rechallenged tumor volumes were calculated every 5 days. Immunohistochemistry and flow cytometry were used to evaluate the T-cell immune responses in ablated tissues and spleens. The tumor-specific immunity was assessed by enzyme-linked immunospot assays. Besides, the cytokine patterns were identified from enzyme-linked immunosorbent assay.ResultsMicrowave ablation plus OK-432 resulted in longer survival than single treatment and protect most surviving mice from tumor rechallenge. Both local and systemic T-cell responses were induced by MWA and were further enhanced by subsequent administration of OK-432. Moreover, the combination of MWA and OK-432 induced stronger tumor-specific immune responses than MWA alone. In addition, OK-432 and MWA synergistically promoted the production of Th1-type but not Th2-type cytokines, and polarized T-cell responses to Th1-dominant state.ConclusionsThe T-cell immune responses were activated by MWA in breast cancer. Furthermore, the combination of MWA and OK-432 induced Th1-type response and elicited specific antitumor immunity.
Highlights
Invasive therapies, such as microwave ablation (MWA), are widely used for the treatment of solid tumors
Combination of MWA and OK‐432 resulted in prolonged survival and enough immunity against tumor rechallenge To assess the antitumor effect of MWA, OK-432 and their combination in breast cancer, their abilities to promote survival were compared
At 10 days after rechallenge, six MWA plus OK-432 treated mice still survivedto allow the evaluation of second tumor, while no mice survived in MWA alone group
Summary
Invasive therapies, such as microwave ablation (MWA), are widely used for the treatment of solid tumors. Previous studies suggest that MWA is feasible for the treatment of small breast cancer, and thermal ablation may induce adaptive antitumor immunity. Recent study has reported that MWA of osteosarcoma can elicit tumor-specific T-cell immune response in a rat model [9]. Li et al J Transl Med (2017) 15:23 the tumor recurrence rate after MWA is similar to that after curative surgical resection [11, 12]. These results indicate that the antitumor immunity induced by MWA is not strong enough to prevent the recurrence of cancers. Additional immunomodulatory strategies are needed to enhance the antitumor immunity
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