Alterations in Immune Response Profile of Tumor-Draining Lymph Nodes after High-Intensity Focused Ultrasound Ablation of Breast Cancer Patients

Abstract

Previous studies have revealed that high-intensity focused ultrasound (HIFU) ablation can trigger an antitumor immune response. The aim of this study was to investigate immune response in tumor-draining lymph nodes (TDLNs) after HIFU treatment. Forty-eight female patients with biopsy-confirmed breast cancer were divided into a control group and an HIFU group. In the control group, 25 patients underwent modified radical mastectomy, but 23 patients in the HIFU group received HIFU ablation of primary cancer, followed by the same operation. Using HE and immunohistochemical staining, the immunologic reactivity pattern and immune cell profile were assessed in paraffin-embedded axillary lymph nodes (ALNs) in all patients. The results showed that ALNs presented more evident immune reactions in the HIFU group than in the control group (100% vs. 64%). Among the ALNs, 78.3% had mixed cellular and humoral immune response, whereas 36% in the control group showed cellular immune response. The numbers of CD3+, CD4+, NK cell, and activated CTLs with Fas ligand+, granzyme+ and perforin+ expression were significantly higher in the ALNs in the HIFU group. It was concluded that HIFU could stimulate potent immune response and significantly increase T cell, activated CTLs and NK cell populations in the TDLNs of breast cancer.

Cancer Immunology: From Molecular Mechanisms to Therapeutic Opportunities

“…Upon HIFU, the authors investigated the immune response efficacy and the ability of HIFU to induce the secretion of several cytotoxic factors (FasL, Perforin, and GranzymeB in ALNs). This study revealed that HIFU stimulates an effective immune response by infiltration of key immune cell subsets, such as CD4+ T and CD57+ T cells, with a concomitant secretion of cytotoxic factors that contrast the further diffusion of metastatic breast cancer cells present in the ALNs [22].…”

Ablative Therapies for Breast Cancer: State of Art

“…The study showed that in the HIFU group, axillary LN had a greater immune reaction than in the control group (100% vs 64%). 71 A phase I clinical trial by the University of Virginia is currently underway to examine the combination of Pembrolizumab either before or after HIFU, in patients with advanced/metastatic BC (R). 72 Complete response was 64.8% in the pembrolizumab-chemotherapy group and 51.2% in the placebo-chemotherapy group.…”

Rational Nanomedicine Design Enhances Clinically Physical Treatment‐Inspired or Combined Immunotherapy

“…After HE and immunohistochemical analysis of axillary lymph nodes, HIFU was observed to stimulate the immune responses of the whole body and significantly increase the number of effector T cells, activated CTLs, and NK cells. [ 124 ]…”