Department of Surgery/Breast Surgical Oncology, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA.
Immunol Invest. 2010;39(1):74-92. doi: 10.3109/08820130903428291.
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.
射频消融（RFA）是一种微创外科手术，在肿瘤的外科治疗中应用日益广泛。数据表明，RFA 可能通过诱导细胞坏死和热休克蛋白（HSP）表达来刺激抗肿瘤免疫。本研究检验了一个假设，即 RFA 导致双向免疫调节。用 RFA、手术切除或假手术处理实验性大鼠乳腺肿瘤。RFA 导致肿瘤边缘的 NK 细胞浸润最高，HSP70 表达增加，半胱氨酸蛋白酶-3 酶激活。在 RFA 和切除治疗的大鼠中，循环调节性 T（Treg）细胞均显著减少，尽管 RFA 组的减少程度较轻。与未治疗的荷瘤大鼠相比，RFA 治疗的大鼠脾细胞对肿瘤细胞裂解物的增殖更强。使用破伤风类毒素体外增殖试验，研究了自身 HSP 对免疫调节的潜在作用，用人类外周白细胞。与 HSP90 或自身抗体单独作用相比，HSP90 加自身抗体对破伤风类毒素的反应明显受到抑制。总之，RFA 虽然不如肿瘤切除有效，但能减少循环中的 Tregs。HSPs 加天然抗体可能通过刺激 Tregs 抑制抗肿瘤反应。因此，如果与 Tregs 抑制联合使用，RFA 可能在癌症治疗中发挥作用。
