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

Surgery. 2009 Mar;145(3):286-93. doi: 10.1016/j.surg.2008.10.010. Epub 2009 Jan 25.


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.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Ablation Techniques / methods*
  • B-Lymphocytes / cytology
  • B-Lymphocytes / immunology
  • Breast Neoplasms / immunology
  • Breast Neoplasms / surgery*
  • CD3 Complex / metabolism
  • CD4 Antigens / metabolism
  • CD8 Antigens / metabolism
  • Cell Movement / physiology
  • Fas Ligand Protein / metabolism
  • Female
  • Granzymes / metabolism
  • Humans
  • Killer Cells, Natural / cytology
  • Killer Cells, Natural / immunology
  • Lymphocytes, Tumor-Infiltrating / cytology*
  • Lymphocytes, Tumor-Infiltrating / immunology*
  • Lymphocytes, Tumor-Infiltrating / metabolism
  • Mastectomy, Modified Radical
  • Middle Aged
  • Perforin / metabolism
  • Prospective Studies
  • T-Lymphocytes, Cytotoxic / cytology
  • T-Lymphocytes, Cytotoxic / immunology
  • Ultrasonics*


  • CD3 Complex
  • CD4 Antigens
  • CD8 Antigens
  • Fas Ligand Protein
  • Perforin
  • Granzymes