Increased infiltration of activated tumor-infiltrating lymphocytes after high intensity focused ultrasound ablation of human breast cancer.

ABSTRACT

BACKGROUND: Previous studies have shown that high intensity focused ultrasound (HIFU) ablation can induce a distinct inflammatory reaction with marked infiltration of lymphocytes after direct tumor destruction. In this study, we investigated the status of tumor-infiltrating lymphocytes (TILs) after HIFU ablation of human breast cancer and explored mechanisms that may be involved in HIFU-triggered, antitumor immune response. METHODS: A total of 48 female patients with biopsy-proven breast cancer were divided randomly into 1 of 2 groups control group (n = 25), in which only modified radical mastectomy was performed, or HIFU group (n = 23), in which HIFU ablation of the primary breast cancer was performed prior to modified radical mastectomy. Using semiquantitative immunohistochemical analysis, tumor-infiltrating T lymphocytes and subsets, B lymphocytes, and natural killer (NK) cells were assessed in all patients. Expression of Fas ligand (FasL), granzyme, and perforin on TILs was also studied in both groups. RESULTS: TILs infiltrated along the margins of the ablated region in all HIFU-treated neoplasms, and the numbers of tumor-infiltrating CD3, CD4, CD8, CD4/CD8, B lymphocytes, and NK cells was increased significantly in the HIFU group. The number of FasL(+), granzyme(+), and perforin(+) TILs was significantly greater in the HIFU group than in the control group. CONCLUSION: HIFU ablation induced marked infiltration of CD3, CD4, CD8, B lymphocytes, and NK cells in the treated breast lesions. The number of FasL(+), granzyme(+), and perforin(+) TILs was significantly increased after HIFU treatment.