Activation of Tumor-Infiltrating Antigen Presenting Cells by High Intensity Focused Ultrasound Ablation of Human Breast Cancer

Previous studies have shown that high intensity focused ultrasound (HIFU) ablation can trigger activation of host antitumor responses after direct tumor destruction. The goal of this study was to investigate the status and functions of tumor-infiltrating antigen presenting cells (APCs) after HIFU ablation of human breast cancer, and to explore the mechanisms regarding HIFU-enhanced antitumor response. Forty-eight women with biopsy-proven breast cancer were divided randomly into a control group (n = 25) and a HIFU group (n = 23). Patients in the control group received modified radical mastectomy, and those in the HIFU group underwent HIFU ablation of primary breast cancer, followed by modified radical mastectomy within 1-2 weeks. Using immunohistochemical analysis, tumor-infiltrating dendritic cells (DCs), macrophages, B lymphocytes and expression of HLA-DR and costimulatory molecules on DCs and macrophages were assessed in all patients. The results showed that APCs infiltrated along the margins of the ablated regions in all HIFU-treated tumors, and numbers of tumor-infiltrating DCs, macrophages and B lymphocytes increased significantly in the HIFU group. Compared with the values in the control group, the percentage of DCs and macrophages expressing HLA-DR, CD80 and CD86 was significantly greater in the HIFU group. There were statistically significant differences between numbers of S-100(+) HLA-DR(+), S-100(+) CD80(+), S-100(+) CD86(+), CD68(+) HLA-DR(+), CD68(+) CD80(+) and CD68(+) CD86(+) cells in the control and HIFU groups, respectively. It was concluded that HIFU ablation induces significant infiltration of APCs within the residual tumor debris in patients with breast cancer, and most of the tumor-infiltrating DCs and macrophages were activated after HIFU ablation.