Immunomodulatory effects of radiofrequency ablation in a breast cancer model.
Radiofrequency ablation (RFA), a minimally invasive surgical procedure has an increasing application in the surgical treatment of tumors. Data indicate that RFA might stimulate anti-cancer immunity possibly through the induction of necrosis and heat shock proteins (HSP) expression. This study tests a hypothesis that RFA leads to bidirectional immunoregulation. Experimental rat breast tumors were treated with RFA, surgical excision or sham operation. RFA resulted in the highest NK cells infiltration, increased HSP70 expression and activation of caspase-3 enzyme in the tumor margins. A significant reduction of the circulatory regulatory T (Treg) cells was found in both RFA- and excision-treated rats, although less pronounced in the RFA-group. The splenocyte proliferation to tumor cell lysate was stronger in the RFA-treated rats in comparison with untreated tumor-bearing rats. The potential role of self-HSP for immunomodulation was examined using in vitro proliferation assay to tetanus toxoid using human peripheral leukocytes. The response to the tetanus toxoid was significantly suppressed by HSP90 plus auto-antibodies versus HSP90 or auto-antibodies alone. In conclusion, RFA reduced the circulatory Tregs although not as efficient as tumor excision. HSPs plus natural antibodies suppress the anti-tumor response probably by stimulating Tregs. Therefore, RFA may play a role in anti-cancer therapy if combined with Tregs suppression.
Todorova
Valentina K
VK
Department of Surgery/Breast Surgical Oncology, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA. todorovavalentinak@uams.edu
Klimberg
V Suzanne
VS
Hennings
Leah
L
Kieber-Emmons
Thomas
T
Pashov
Anastas
A
D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology; D001943:Breast Neoplasms; D053148:Caspase 3 / Q000378:metabolism; D017115:Catheter Ablation; D002452:Cell Count; D049109:Cell Proliferation; D004789:Enzyme Activation; D005260:Female; D018840:HSP70 Heat-Shock Proteins / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D056747:Immunomodulation; D007694:Killer Cells, Natural / Q000473:pathology; D008325:Mammary Neoplasms, Experimental / Q000276:immunology* / Q000473:pathology / Q000601:surgery*; D015412:Mastectomy, Segmental; D051381:Rats; D050378:T-Lymphocytes, Regulatory / Q000473:pathology; D019139:Tumor Escape
D000951:Antigens, Neoplasm; D018840:HSP70 Heat-Shock Proteins; D053148:Caspase 3