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


CONCLUSIONS
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.
Lu
Pei
P
Clinical Center for Tumor Therapy of 2nd Affiliated Hospital, Institute of Ultrasonic Engineering in Medicine, Chongqing Medical University, Chongqing, China.
Zhu
Xue-Qiang
XQ
Xu
Zhong-Lin
ZL
Zhou
Qiang
Q
Zhang
Jun
J
Wu
Feng
F
D055011:Ablation Techniques / Q000379:methods*; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology; D001943:Breast Neoplasms / Q000276:immunology / Q000601:surgery*; D017252:CD3 Complex / Q000378:metabolism; D015704:CD4 Antigens / Q000378:metabolism; D016827:CD8 Antigens / Q000378:metabolism; D002465:Cell Movement / Q000502:physiology; D053222:Fas Ligand Protein / Q000378:metabolism; D005260:Female; D053804:Granzymes / Q000378:metabolism; D006801:Humans; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology; D016246:Lymphocytes, Tumor-Infiltrating / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D015411:Mastectomy, Modified Radical; D008875:Middle Aged; D054353:Perforin / Q000378:metabolism; D011446:Prospective Studies; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology / Q000276:immunology; D014465:Ultrasonics
D017252:CD3 Complex; D015704:CD4 Antigens; D016827:CD8 Antigens; D053222:Fas Ligand Protein; D054353:Perforin; D053804:Granzymes